<div class="section fw-banner--picture image" id="banner"><picture><source media="(min-width: 64.0625em)" srcset="../../../images/banners/100_voices_of_hope-1800x600.jpg" type="image/jpeg"/><source media="(min-width: 40em)" srcset="../../../images/banners/100_voices_of_hope-1200x400.jpg" type="image/jpeg"/><source media="(max-width: 39.9375em)" srcset="../../../images/banners/100_voices_of_hope-768x512.jpg" type="image/jpeg"/><img alt="" src="../../../images/banners/100_voices_of_hope-1800x600.jpg"/></picture></div></header><main><div class="content-top"><div class="section breadcrumbs"><div class="row"><div class="layout"><ul itemscope="itemscope" itemtype="http://schema.org/BreadcrumbList"><li itemprop="itemListElement" itemscope="itemscope" itemtype="http://schema.org/ListItem"><a href="../../../index.html" itemprop="item"><span itemprop="name">Home</span></a><meta content="1" itemprop="position"/></li><li itemprop="itemListElement" itemscope="itemscope" itemtype="http://schema.org/ListItem"><a href="../../index.html" itemprop="item"><span itemprop="name">Community</span></a><meta content="2" itemprop="position"/></li><li itemprop="itemListElement" itemscope="itemscope" itemtype="http://schema.org/ListItem"><a href="../index.html" itemprop="item"><span itemprop="name">Events</span></a><meta content="3" itemprop="position"/></li><li itemprop="itemListElement" itemscope="itemscope" itemtype="http://schema.org/ListItem"><a href="index.html" itemprop="item"><span itemprop="name">100 Voices of Hope</span></a><meta content="4" itemprop="position"/></li><li class="current" itemprop="itemListElement" itemscope="itemscope" itemtype="http://schema.org/ListItem"><span itemprop="name">Hunch History</span><meta content="5" itemprop="position"/></li></ul></div></div></div><div class="section page-title bg-none"><div class="row"><div class="layout"><h1>100 Voices of Hope Hunch History</h1></div></div></div></div><div id="main-content"><div class="collapsed bg-none section" id="content"><div class="row"><div class="layout"><div class="text"><h2>Your voices have been heard</h2><p>What’s in a hunch? Every year, the 100 Voices of Hope organization invites the experts at IU Simon Comprehensive Cancer Center to explore their “hunches” on new ways to treat, diagnose, and prevent breast cancer—and your gifts help fund their research.</p><p><a class="button" href="https://www.facebook.com/100VoicesOfHopeIUSimonCancerCenter/">Facebook</a> <a class="button" href="subscribe.html">Email Updates</a> <a class="button" href="../../../contact/index.html">Contact Us</a></p></div></div><!-- /.layout --></div></div><div class="bg-none section"><div class="row"><div class="layout"><div class="accordion" data-accordion="" id="accordion-0--1617265845"><div class="accordion-item"><h3><button aria-controls="panel-0--1617265845-1" class="accordion-title" id="panel-0--1617265845-1-heading"><span class="accordion-label has-content">Hunch #35: Hitting the Master Switch: Targeting IL1RAP in Aggressive Breast Tumors (2026)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-0--1617265845-1-heading" class="accordion-content" data-tab-content="" id="panel-0--1617265845-1" role="region"><p><a href="https://cancer.iu.edu/about/members/bio/31045">Pravin Kaumaya, PhD</a></p><p>For patients with aggressive triple-negative breast cancer, the goal of chemotherapy and immunotherapy is to eliminate metastasis before tumors can grow large enough to become life-threatening. While those therapies cure many patients, some cancers become resistant to standard chemotherapy and learn to ‘hide’ from the immune system.  This proposal aims to stop this often-fatal process by targeting the inflammation that cancer cells cleverly use to grow and evade the immune system. Chronic inflammation, mediated by the Interleukin-1 (IL-1) signaling pathway, fuels this resistance. IL-1 is known to promote tumor growth, invasion, and the formation of distant metastases. We plan to block a specific protein “IL1RAP”, which acts as a master switch for pro-cancer inflammation. IL1RAP is found not only on the tumor cells, but also on the protective cells surrounding the tumor. In short, IL1RAP is a "one to watch" in the breast cancer field, representing a promising new axis for future targeted therapies aimed at defeating the most treatment-resistant forms of the disease. By neutralizing this protein, we can achieve two things. First, we suppress the cancer’s ability to resist drugs and grow. Second, we re-activate the body’s own immune cells to attack the tumor. The goal is to prove that this new, targeted strategy can dramatically shrink tumors, enhance the power of existing treatments, and ultimately prevent cancer from establishing dangerous new growth sites in vital organs like the lungs and bone. In this project, we will first analyze tumor specimens from patients with metastatic TNBC to correlate the level of IL1RAP expression (on both tumor and surrounding cells) with clinical outcomes. Next, we will test the impact of blocking IL1RAP alone and in combination with other therapies using mouse models of aggressive breast cancer. The mouse studies will measure the impact on growth of the primary tumor and the development of metastasis.</p></div><div class="accordion-item"><h3><button aria-controls="panel-0--1617265845-2" class="accordion-title" id="panel-0--1617265845-2-heading"><span class="accordion-label has-content">Hunch #34: Double Defense: Combining Radiation and DNase-I to Halt Metastasis (2026)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-0--1617265845-2-heading" class="accordion-content" data-tab-content="" id="panel-0--1617265845-2" role="region"><p><a href="https://cancer.iu.edu/about/members/bio/32705">Siri Tadepalli, PhD</a></p><p>Radiation therapy is an essential part of breast cancer treatment and helps prevent local tumor recurrence after surgery. For decades, radiation has been viewed as a cure for the primary tumor, with the goal of eradicating every cancer cell in the treated area, including those that may have spread to nearby lymph nodes. However, in pursuing this goal, nearby healthy tissues in the chest wall and the upper portions of the lung are inevitably exposed to radiation. Our recent work suggests this collateral radiation exposure – which was long-considered harmless – can alter immune cell recruitment within these healthy tissues and influence how the body responds to treatment. Healthy tissues (once thought to be unaffected) respond to radiation, releasing distress signals that alter the body’s immune balance. These signals recruit immune cells called neutrophils, which respond as if the irradiated tissue were wounded or infected. In the process, they release sticky DNA–protein webs known as neutrophil extracellular traps (NETs). While NETs normally help trap bacteria during infection, in cancer they can have unintended effects. The lung, which continuously filters the blood, becomes a natural site where these NETs accumulate and can capture circulating tumor cells (CTCs) shed from the primary breast tumor. Once trapped, these cells may anchor, survive, and eventually form new metastatic colonies. Thus, the very act of protecting a patient with radiation may inadvertently influence immune responses in healthy tissues that could shape cancer’s ability to spread. Our project will test this idea using mouse models of breast cancer to determine whether radiation to healthy tissue alters neutrophil recruitment in the lung and triggers NET formation, and whether blocking these traps can reduce metastasis. We will use DNase-I, an FDA-approved enzyme that safely dissolves NETs and is already used to treat cystic fibrosis. By pairing standard radiation therapy with a short course of DNase-I, we aim to preserve the tumor-killing benefits of radiation while minimizing its unintended systemic effects. If successful, this work will provide new insight into how radiation affects immune function in healthy tissues and may guide strategies to prevent unwanted side effects such as metastasis. Ultimately, it could lead to a simple, immediately translatable strategy to improve long-term survival for breast cancer patients.</p></div><div class="accordion-item"><h3><button aria-controls="panel-0--1617265845-3" class="accordion-title" id="panel-0--1617265845-3-heading"><span class="accordion-label has-content">Hunch #33: Catching Metastatic Breast Cancer by the Tail: Zebrafish Lead the Way (2026)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-0--1617265845-3-heading" class="accordion-content" data-tab-content="" id="panel-0--1617265845-3" role="region"><p><a href="https://cancer.iu.edu/about/members/bio/32638">Yann Gibert, PhD</a></p><p>Breast cancer remains one of the leading causes of cancer-related death in women, especially when it metastasizes to other parts of the body. To help develop better treatments, we are testing a promising new drug, called RuSPTC, that targets breast cancer in two powerful ways: it blocks the cancer’s ability to spread, and it also kills the cancer cells directly. RuSPTC was created by an investigator at UC Santa Barbara. IU investigators will test this new treatment in cancer cell cultures and live zebrafish. Zebrafish may seem like an unlikely model for cancer research, but they are often used to study human breast cancer biology and migration because they share some important genes and biological processes with humans. Their embryos are transparent, which allows researchers to see and track cancer cells as they grow and spread in real time. Our project has two goals. First, we will test how well RuSPTC kills breast cancer cells and stops them from migrating in a petri dish. Second, we will inject human breast cancer cells into zebrafish embryos and treat them with RuSPTC to see how the drug affects tumor growth and cancer spread in a living organism. We will also make sure the drug is not harmful to developing fish at effective doses. If successful, this project could lay the foundation for a new type of breast cancer treatment, especially for aggressive forms like triple-negative breast cancer. It also demonstrates how zebrafish can speed up cancer research and help identify new therapies more efficiently.</p></div><div class="accordion-item"><h3><button aria-controls="panel-0--1617265845-4" class="accordion-title" id="panel-0--1617265845-4-heading"><span class="accordion-label has-content">Hunch #32: Molecules and Mutations: Establishing a new metastatic model of HER2 breast cancer (2025)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-0--1617265845-4-heading" class="accordion-content" data-tab-content="" id="panel-0--1617265845-4" role="region"><p><a href="https://cancer.iu.edu/about/members/bio/31864">Ana Sofia Mendes Leal, PharmD, PhD</a></p><p>Our hunch hopes to establish a new metastatic model of HER2 breast cancer to enhance therapeutic options. Despite accounting for only 15-20% of breast cancers, HER2 positive breast cancers are one of the breast cancer types more likely to progress. HER2 breast cancer metastasis often acquires other mutations besides HER2, including NF1 mutations. NF1 mutations allow cancer cells to easily expand and resist targeted treatment to HER2. Currently, there are no mouse models that mimic HER2 disease progression and metastasis with NF1 mutations. This hunch proposes to create a simple and reproducible model for HER2 metastasis with NF1 mutations, which can be used to test a therapeutic agent. Our lab has generated a small molecule, MSU42011, which is a derivative of the approved anticancer therapy bexarotene. Bexarotene has been effective at reducing HER2 positive mouse breast tumors. MSU42011 is more potent than bexarotene and has less side effects. MSU42011 is extremely effective at reducing tumor growth in a neurologic model of cancer (known as a malignant peripheral nerve sheath tumor) that is dependent on NF1. Once we have the mouse model for the metastatic disease of HER2 breast cancers which includes the NF1 mutations, MSU42011 will be tested for its ability to reduce HER2 positive tumor burden.</p></div><div class="accordion-item"><h3><button aria-controls="panel-0--1617265845-5" class="accordion-title" id="panel-0--1617265845-5-heading"><span class="accordion-label has-content">Hunch #31: A LANTERN Lights the Way: Targeted delivery of chemotherapy and siRNA for enhanced treatment of metastatic breast cancer (2025)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-0--1617265845-5-heading" class="accordion-content" data-tab-content="" id="panel-0--1617265845-5" role="region"><p><a href="https://cancer.iu.edu/about/members/bio/29487">Wen Zhang, PhD</a></p><p>Metastatic breast cancer is particularly difficult to treat because current therapies often cause harmful side effects and don't always precisely target cancer cells. We are developing an advanced drug delivery system called LANTERN (L-nucleic Acid Nanoparticles for Targeted Engineering and Robust Nanomedicine), which uses tiny, nano-sized particles made from a special form of nucleic acid, which is a fundamental component of DNA and RNA. These particles are highly stable and can carry multiple treatments. To ensure the treatment reaches cancer cells specifically, LANTERN can be equipped with natural molecules, like folic acid, that help it recognize and bind to cancer cells more effectively. Once delivered, LANTERN would release FDA-approved chemotherapy drugs like Paclitaxel and Doxorubicin, along with siRNA, a therapy that blocks genes involved in cancer growth and spread. By focusing the treatment directly on cancer cells, LANTERN reduces the risk of harming healthy cells, potentially making the treatment more effective and causing fewer side effects. With LANTERN, we hope to bring new, safer and more effective treatment options to those battling metastatic breast cancer.</p></div><div class="accordion-item"><h3><button aria-controls="panel-0--1617265845-6" class="accordion-title" id="panel-0--1617265845-6-heading"><span class="accordion-label has-content">Hunch #30: Designer Genes: Targeting gamma delta T-cell receptors using CRISPR nanoformulations (2024)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-0--1617265845-6-heading" class="accordion-content" data-tab-content="" id="panel-0--1617265845-6" role="region"><p><a href="https://cancer.iu.edu/about/members/bio/29745" rel="noopener" target="_blank">Reza Shahbazi, PhD, MS </a></p><p>Triple negative breast cancer (TNBC) is a challenging form of cancer that doesn't respond well to traditional treatments. Immunotherapy is a promising approach that involves using the body's immune system to fight cancer. One type of immunotherapy uses special immune cells called gamma delta (γδ) T cells, which have unique abilities to recognize and attack cancer cells. However, there are challenges, such as finding the right targets on cancer cells for these immune cells to attack effectively. In this project, we are using tiny particles released by cancer cells called exosomes to help identify these targets on TNBC cells. These exosomes carry information about the cancer cells' surface proteins. Previously we studied interaction of TNBC exosomes with T cells and discovered specific codes that can guide γδ T cells to target TNBC cells effectively. In the next phase of this project, we will use advanced gene-editing techniques to modify γδ T cells. We will insert specific codes into the γδ T cells, essentially arming them with the knowledge to recognize and destroy TNBC cells. Our team will then carefully test these genetically engineered γδ T cells to observe if they may effectively kill TNBC cells.</p></div><div class="accordion-item"><h3><button aria-controls="panel-0--1617265845-7" class="accordion-title" id="panel-0--1617265845-7-heading"><span class="accordion-label has-content">Hunch #29: Vaccination is the best shot: Combination vaccine therapy for aggressive breast cancer (2024)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-0--1617265845-7-heading" class="accordion-content" data-tab-content="" id="panel-0--1617265845-7" role="region"><p><a href="https://cancer.iu.edu/about/members/bio/31045" rel="noopener" target="_blank">Pravin Kaumaya, PhD</a></p><p>Breast cancer is a highly variable disease. Immune checkpoint inhibitors are a type of immunotherapy that uses the immune system’s natural ability to fight cancer. Immune checkpoint inhibitors have been effective in the treatment of about 40% of triple negative breast cancers that express the protein PD-L1. We take a different approach to immune therapy. Rather than infusing a lab-made antibody, we propose a vaccine that triggers the body’s B-cells to produce the right antibody that will attack the cancer cells. This approach has several potential advantages, including: (1) tumor specificity; and (2) activation of immune responses against other proteins that are selectively expressed by tumor cells. We have already tested a vaccine against HER2 in an early clinical trial. The results were encouraging with minimal toxicity and prolonged production of HER2-targeted antibodies. We have now developed a portfolio of several immune checkpoint vaccines (PD-1, PD-L1, CTLA-4, TIGIT and LAG 3) that are intended to be used in combination immunotherapies. Unlike monoclonal anti-PD1 antibody therapy, a combination vaccine therapies (chimeric B-cell peptide) proposed in our project are designed to stimulate a sustained immune response with minimal toxicity. We have prioritized TIGIT (one of our developed immune checkpoint vaccines) as a target of immunotherapy for invasive breast cancer to be used in combination with other vaccines for both triple negative and HER2+ disease. The proposed preclinical studies will be used to test these combinations prior to planned phase 1 clinical trials.</p></div><div class="accordion-item"><h3><button aria-controls="panel-0--1617265845-8" class="accordion-title" id="panel-0--1617265845-8-heading"><span class="accordion-label has-content"> Hunch #28: When Sugar is Not Sweet: Inhibiting Sugar to Make Cancer Treatment More Effective (2023)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-0--1617265845-8-heading" class="accordion-content" data-tab-content="" id="panel-0--1617265845-8" role="region"><p><a href="https://medicine.iu.edu/faculty/44735/doud-emma">Emma Doud, PhD</a> </p><p>Cancer cells have many tricky ways to avoid the immune system and become resistant to treatment. All cells have proteins on their surfaces – and changing these proteins can impact the immune system’s ability to recognize the cell and may impact the response to antibody-based treatments. Very recently, we’ve learned that in patients with metastatic breast cancer, The proteins on tumor cells contain more of a specific sugar molecule (called FAGL1) to their surface proteins. When more of these sugars are present, the disease presents as more aggressive – and survival rates decrease. The sugar molecules make it hard for antibodies to recognize the tumor, and they also promote inflammation and growth in the tumor. The goal of this research proposal is to use a technique called mass spectrometry to identify which cell surface proteins carry the FAGL1 modification in breast cancer cells growing in the lab and on patient tumor samples. Then we will study whether blocking this sugar molecule could be useful as a breast cancer therapy.</p></div><div class="accordion-item"><h3><button aria-controls="panel-0--1617265845-9" class="accordion-title" id="panel-0--1617265845-9-heading"><span class="accordion-label has-content">Hunch #27: Sending the Right Message: Identifying the Role of Triple Negative Breast Cancer-Derived Exosomes in Immunosuppression and Metastasis (2023)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-0--1617265845-9-heading" class="accordion-content" data-tab-content="" id="panel-0--1617265845-9" role="region"><p><a href="https://medicine.iu.edu/faculty/59877/shahbazi-reza">Reza Shahbazi, PhD, MS</a> </p><p>Our immune system recognizes and attacks foreign pathogens (bacteria, viruses) as well as tumors. The immune system has several different kinds of cells with very specialized functions. T cells are a part of the immune system that focuses on specific foreign particles. T cells play a critical part in immunity to foreign substances. Each T cell recognizes only one target – your body makes hundreds of thousands of T cells that are never used. When a T cell recognizes its target, it begins the attack. It also suppresses immune cells called (Tregs) that would stop the attack.</p><p>In this project, we will study the role of exosomes (tiny bubbles that pinch the cell membrane) that carry messages to stop the immune response. These tiny particles can find their way to the target immune cell using their specific surface proteins. They carry unique messages including RNA, DNA, or protein signals that impact the function of the target cell. Recently, we have seen a very specific interaction between metastatic breast cancer exosomes and T cells. We will use powerful new technology to study the messages in exosomes from individual breast cancer cells, sequencing the message in one exosome at a time. We are hopeful that this detailed study would lead us to identify potential molecules and genes that regulate the immune response. Once we’ve identified the messages that inhibit the immune response, we will engineer T cells that lack that critical function so we can study how to turn the function back on. We believe that the successful development of more potent engineered T cells would help us provide non-invasive therapies for both early and late-stage metastatic breast cancer patients.</p></div><div class="accordion-item"><h3><button aria-controls="panel-0--1617265845-10" class="accordion-title" id="panel-0--1617265845-10-heading"><span class="accordion-label has-content">Hunch #26: Cutting your cell service: The IL-9 Pathway as a Therapeutic Target in Metastatic Breast Cancer (2023)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-0--1617265845-10-heading" class="accordion-content" data-tab-content="" id="panel-0--1617265845-10" role="region"><p><a href="https://cancer.iu.edu/about/members/bio.html?id=1196">Mark Kaplan, PhD</a></p><p>Communication is a commodity in the 21st century. What is true in our society is also true at the molecular level in tumors. Central to the development of cancer and the movement of cancer to distant parts of the body is the ability of cells to communicate. In fact, the communication among cells in the immune system within the local tumor environment determines the rate of tumor growth and the ability of the tumor to metastasize. Current immune-based therapies, such as the anti-cancer drugs routinely advertised on television, have had remarkable impact in lung cancer. These immune therapies were developed by targeting “off signals” communicated between immune cells. This hunch is based on one of those “off signals” called a cytokine – a molecule that is tossed into the environment by one cell as a means of communicating to other cells. We found that blocking this cytokine, called IL-9, impairs the ability of metastases to form in the lung, a common site of tumor spread. We further found that the cells in the lung that respond to IL-9 share features with cells in the breast tumor. The studies in this proposal will test the effects of blocking IL-9 alone or in combination with other standard of care therapies for breast cancer. We will further test whether blocking the signal triggered by IL-9 controls tumor growth and metastasis. The work would provide the basis for several approaches to translation into patients. First, IL-9 blocking antibodies were developed and tested in clinical trials for asthma years ago. They have never been tested for efficacy in cancer. Second, drugs that block the signals triggered by IL-9 are being used in the clinic for a variety of autoimmune and allergic diseases. Our data suggests they might also be useful in modifying responses to tumor. Finally, the cells that contribute to IL-9 production can be targeted to modify immune responses. The proposed studies will lay the foundation for using therapies already developed for other purposes as an adjuvant to breast cancer treatment.</p></div></div></div><!-- /.layout --></div></div><div class="breakout bg-crimson bg-dark section"><div class="row"><div class="layout"><div class="callout"><div class="content"><p>The road to a cure starts with learning how and why breast cancer develops, how it behaves at different stages of a woman’s life, and how it uniquely affects women from different racial and ethnic groups.</p></div></div></div><!-- /.layout --></div></div><div class="bg-none section"><div class="row"><div class="layout"><div class="accordion" data-accordion="" id="accordion-1--1617265845"><div class="accordion-item"><h3><button aria-controls="panel-1--1617265845-1" class="accordion-title" id="panel-1--1617265845-1-heading"><span class="accordion-label has-content">Hunch #25: Making Cancer Cells Feel at Home: Identifying the Proteins that Drive Metastasis (2022)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-1--1617265845-1-heading" class="accordion-content" data-tab-content="" id="panel-1--1617265845-1" role="region"><p><a href="../../../about/members/bio/1111/index.html">Hari Nakshatri, PhD</a></p><p>Recent advances in genomic research raised hope of identifying a specific genetic abnormality in cancer metastasis that differentiates it from the primary tumor. The hope was we could take advantage of this abnormality to specifically target metastasis.<br/><br/>Unfortunately, that approach hasn’t worked, despite sequencing metastatic tissues from multiple organs from the same donor and sequencing the primary tumor and metastasis from the same patient. Now we must think about the metastatic process differently.<br/><br/>One possibility is that the ability to metastasize is hardwired in the primary tumor from the beginning. If that is the case, we won’t find it by comparing primary to metastasis. Instead, we need to look for genetic abnormalities in the primary tumor that enable metastasis.<br/><br/>In our studies, we found that when breast cells obtained from a healthy donor were made cancerous upon introduction of one genetic abnormality (oncogene) they developed tumors in mice that did not metastasize to lungs. However, cells from the same donor when made cancerous by a different oncogene, developed tumors that did metastasize to lungs<br/><br/>When we compared proteins in the primary tumor and metastasis from the second model, there were minimal differences—just like the human studies. Our hypothesis is that cells that became cancerous by the second oncogene but not the first oncogene secrete proteins that are released into the bloodstream.<br/><br/>These proteins then go to the lung and modify the lung in such a way that it becomes hospitable for the cancer cells to come, attach, and grow. In other words, these proteins make a section of lung “breast-like” so that breast cancer cells feel at home.<br/><br/>Through sophisticated techniques of proteomics, we would like to identify those proteins that are expressed differently in our models and determine how they modify the metastatic site to welcome cells from the primary site. These efforts should lead to the development of new drug targets for metastasis.</p></div><div class="accordion-item"><h3><button aria-controls="panel-1--1617265845-2" class="accordion-title" id="panel-1--1617265845-2-heading"><span class="accordion-label has-content">Hunch #24: YAP-TAZ PROTAC Degraders for Treatment of Triple-Negative Breast Cancer Metastasis (2022)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-1--1617265845-2-heading" class="accordion-content" data-tab-content="" id="panel-1--1617265845-2" role="region"><p><a href="../../../about/members/bio/3531/index.html">Samy Meroueh, PhD</a><br/><br/>Healthy cells hold on tightly to the cells next to them. When they lose contact with their neighbors, they die. Cancer cells need to let go of their neighbors to move into the blood stream and metastasize. How do cancer cells let go without dying?<br/><br/>Proteins known as YAP and TAZ protect cancer cells from dying when they are ‘on their own’. YAP and TAZ also suppress the immune system’s ability to recognize and kill the cancer cells. In healthy cells that are in contact with their neighbors, YAP and TAZ are turned off. The goal of this proposal is to turn off YAP and TAZ in cancer cells.<br/><br/>Rather than developing a drug to interact with the proteins and inhibit their function, this group takes a different approach, using PROTAC degraders, a new technology that could revolutionize cancer drug development. Several PROTACs have been approved for clinical trials. PROTACs take advantage of the cell’s own recycling machinery to degrade or eliminate the target, in this case YAP and TAZ.<br/><br/>The lab has developed a PROTAC degrader that is capable of eliminating YAP and TAZ from triple-negative breast cancer cells at nanomolar (really low) doses. We expect our PROTACs to prevent triple-negative breast cancer metastasis in animal studies. Because PROTACs are catalysts, and they do not compete with their target, very small doses are required for treatment, making them much easier to develop into drugs for patients.<br/><br/>Funding will enable us to test our existing PROTACs (TED-650 or TED-674) in animal studies of cancer metastasis. If successful, the PROTACs will become candidates for investigational new drug studies and eventually clinical trials for the prevention and treatment of cancer metastasis, and for combination studies to inhibit tumor growth.</p></div><div class="accordion-item"><h3><button aria-controls="panel-1--1617265845-3" class="accordion-title" id="panel-1--1617265845-3-heading"><span class="accordion-label has-content">Hunch #23: Ion Transport Inhibitors and Therapy-Resistant Metastatic Triple Negative Breast Cancer (2021)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-1--1617265845-3-heading" class="accordion-content" data-tab-content="" id="panel-1--1617265845-3" role="region"><p>Sunil Badve, MD and Yesim Polar, PhD<br/><br/>There is no targeted therapy for patients with triple negative breast cancer (TNBC), one of the most aggressive forms of the disease. The use of chemotherapy prior to surgery can lead to a dramatic reduction in tumor size or even complete disappearance of a tumor, which is called pathologic complete response or pCR. pCR is associated with excellent long-term survival.<br/><br/>To understand the biologic basis of pCR, this lab has compared gene expression patterns (think of them as gene fingerprints) in patients who achieved a pCR with chemotherapy and those whose tumors were resistant. This led the team to identify “ion transport” as a major pathway associated with chemotherapy resistance.<br/><br/>This hunch will target the ion transport pathway as a way to control metastatic TNBC. ‘Ion transport’ is a major way cells carry information from inside to outside the cell, and vice versa. Think of it as the information highway for cells.</p><p>Cancer cells foul their immediate environment and make it very acidic for normal cells. This acidity is controlled by ion-transporters. We can alter the levels of these transporters either by genetically manipulating the cells or by treating them with drugs.<br/><br/>Recently, this team collaborated with a researcher at the University of Oxford who documented that S0859, a drug that disrupts ion transport, alters acidity in the cancer cell’s environment and suppresses tumor growth. The Oxford study was conducted in 10 cell lines, and only one was a TNBC cell line.<br/><br/>Funding this hunch would allow our researchers to investigate the utility of S0859 in a broad range of TNBC cell lines and patient-derived animal models.</p></div><div class="accordion-item"><h3><button aria-controls="panel-1--1617265845-4" class="accordion-title" id="panel-1--1617265845-4-heading"><span class="accordion-label has-content">Hunch #22: Induced Tumor-Suppressing Cells and their Therapeutic Use (2021)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-1--1617265845-4-heading" class="accordion-content" data-tab-content="" id="panel-1--1617265845-4" role="region"><p><a href="../../../about/members/bio/3984/index.html"> Hiroki Yokota, PhD</a><br/><br/>Survival of the fittest is a dominant principle in nature. Fish compete for food and the best habitat in the ocean; trees compete for water, nutrients and sunlight. Cells in our body face the same pressures—they compete for space, nutrients, and oxygen, too.<br/><br/>Our question is a simple one with big implications: Can we generate specifically engineered cells that are ‘more fit’ and can eliminate less-fit cancer cells?<br/><br/>Until recently, that seemed impossible. In 2012, the Nobel Prize was awarded for the creation of ‘induced pluripotent cells’ (iPS cells). iPS technology allows researchers to revert cells back to stem cells and then use those stem cells to produce specialized cell types. It would be similar to taking a cake and reverting it back to flour, and then changing it to another food, like cookies.<br/><br/>This discovery challenged a fundamental concept of development and opened new possibilities in regenerative medicine. This lab has used the same technique that created iPS cells to engineer “induced tumor-suppressing” cells (iTS cells). Their laboratory work has shown iTS cells can effectively kill breast cancer cells, as well as prostate and pancreatic cancer cells, likely by secreting certain proteins which kill less-fit cancer cells.<br/><br/>These factors could potentially be developed as cancer therapies, but the concept needs to be proven. Funding this project would allow for further preclinical study and mock pilot clinical trial testing using iTS cells in animal models.<br/><br/>Successful completion of the proposed study will move us closer to clinical testing of this unique potential treatment option.</p></div><div class="accordion-item"><h3><button aria-controls="panel-1--1617265845-5" class="accordion-title" id="panel-1--1617265845-5-heading"><span class="accordion-label has-content">Hunch #21: Searching for a HUNK inhibitor (2020)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-1--1617265845-5-heading" class="accordion-content" data-tab-content="" id="panel-1--1617265845-5" role="region"><p><a href="../../../about/members/bio/26885/index.html">Elizabeth Yeh, PhD</a><br/><br/>Metastatic disease is currently incurable. We have identified a molecule, called HUNK (Hormonal Upregulated Neuassociated Kinase), that is critical for breast cancers to metastasize.</p><p>When we eliminate HUNK or block its function in pre-clinical models, the cancers don’t metastasize. This suggests that targeting HUNK may be a useful treatment strategy. Unfortunately, there are no known chemical inhibitors of HUNK. Until recently it wasn’t possible to screen drugs for activity against HUNK. We have solved that problem and have already developed a reliable test capable of screening thousands of compounds.<br/><br/>The goal of this proposal is to streamline the identification of a clinically relevant HUNK inhibitor by using a modified “me too” drug discovery approach. We will take FDA-approved agents already being applied to treat cancer and test them for their ability to bind to HUNK.<br/><br/>We will then test whether those that bind HUNK block its activity. Because the agents we want to test are already FDA approved, clinical application will be streamlined.<br/><br/>The major benefit of this approach is that “re-positioning” FDA approved agents will cut out the time consuming and expensive (multi-million dollar) process generally associated with traditional drug discovery.</p></div><div class="accordion-item"><h3><button aria-controls="panel-1--1617265845-6" class="accordion-title" id="panel-1--1617265845-6-heading"><span class="accordion-label has-content">Hunch #20: Using acoustic and fluid mechanics to diagnose breast cancer metastasis (2020)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-1--1617265845-6-heading" class="accordion-content" data-tab-content="" id="panel-1--1617265845-6" role="region"><p><a href="../../../about/members/bio/25106/index.html">Feng Guo, PhD</a> and <a href="../../../about/members/bio/1160/index.html">Kenneth Nephew, PhD</a><br/><br/>More than 90 percent of cancer deaths are the result of metastatic disease. Cancer cells spread through blood as circulating tumor cells (CTCs) and lodge at distant organs to form metastasis. CTCs can be detected in the blood in a test often called a “liquid biopsy”.<br/><br/>Primary tumors may shed millions of tumor cells into the bloodstream every day; however, only hundreds of cells or less adhere at distant tissue sites. That is to say that only a small fraction of CTCs can form metastasis.<br/><br/>Unfortunately, we can’t determine which of the CTCs will form metastasis and which won’t. Thus, the objective of this proposal is to develop a method that not only separates and identifies a patient’s CTCs, but also measures how well they can stick to distant tissues.<br/><br/>The research team hopes to determine which characteristics of a cell make it more “sticky” thereby creating a method to identify the cells more likely to form metastasis.<br/><br/>This proposal is a partnership between two labs. One lab specializes in acoustic and microfluidic technologies for isolating cells and measuring their stickiness. The other lab has extensive expertise in breast cancer biology and animal models of metastasis. This multidisciplinary team will test the hypothesis that the CTC stickiness is a good predictor of their ability to form metastasis.<br/><br/>The team aims to:</p><ol><li>Build an acoustofluidic system to isolate and profile the stickiness of CTCs; and</li><li>Validate this system using breast cancer patient blood samples and animal models.</li></ol><p>The proposed project will contribute to the development of a new method for diagnosing cancer metastasis that could save lives.</p></div></div></div><!-- /.layout --></div></div><div class="breakout carousel-features bg-gray section"><div class="row"><div class="layout"><h3 class="section-title">Names to know: Researchers awarded hunch funding</h3><div class=" grid thirds"><div class="grid-item"><div class="feature"><figure class="media image media--border" itemscope="itemscope" itemtype="http://schema.org/ImageObject"><img alt="" src="../../../images/people/hiroki_yokota-768x768.png"/></figure><div class="content"><h4 class="title">Hiroki Yokota, PhD</h4><p><p><a class="button" href="../../../about/members/bio/3984/index.html">Learn More</a></p></p></div></div></div><div class="grid-item"><div class="feature"><figure class="media image media--border" itemscope="itemscope" itemtype="http://schema.org/ImageObject"><img alt="" src="../../../images/people/tarah-ballinger-labcoat-768x768.jpg"/></figure><div class="content"><h4 class="title">Tarah Ballinger, MD</h4><p><p><a class="button" href="../../../about/members/bio/22023/index.html">Learn More</a></p></p></div></div></div><div class="grid-item"><div class="feature"><figure class="media image media--border" itemscope="itemscope" itemtype="http://schema.org/ImageObject"><img alt="Photo of breast cancer researcher Chunhai Hao, MD, PhD" src="../../../images/people/chunhai_hao-768x768.jpg"/></figure><div class="content"><h4 class="title">Chunhai Hao, MD, PhD</h4><p><p><a class="button" href="../../../about/members/bio/23404/index.html">Learn More</a></p></p></div></div></div><div class="grid-item"><div class="feature"><figure class="media image media--border" itemscope="itemscope" itemtype="http://schema.org/ImageObject"><img alt="Photo of breast cancer researcher Kenneth Nephew, PhD" src="../../../images/people/kenneth-nephew-768x768.jpg"/></figure><div class="content"><h4 class="title">Kenneth Nephew, PhD </h4><p><p><a class="button" href="../../../about/members/bio/26983/index.html">Learn More</a></p></p></div></div></div><div class="grid-item"><div class="feature"><figure class="media image media--border" itemscope="itemscope" itemtype="http://schema.org/ImageObject"><img alt="" src="../../../images/people/hari_nakshatri-768x768.jpg"/></figure><div class="content"><h4 class="title">Harikrishna Nakshatri, PhD</h4><p><p><a class="button" href="../../../about/members/bio/1111/index.html">Learn More</a></p></p></div></div></div><div class="grid-item"><div class="feature"><figure class="media image media--border" itemscope="itemscope" itemtype="http://schema.org/ImageObject"><img alt="" src="../../../images/people/kathy_miller-768x768.jpg"/></figure><div class="content"><h4 class="title">Kathy Miller, MD</h4><p><p><a class="button" href="../../../about/members/bio/3008/index.html">Learn More</a></p></p></div></div></div><div class="grid-item"><div class="feature"><figure class="media image media--border" itemscope="itemscope" itemtype="http://schema.org/ImageObject"><img alt="" src="../../../images/people/bryan_schneider-768x768.jpg"/></figure><div class="content"><h4 class="title">Bryan Schneider, MD</h4><p><p><a class="button" href="../../../about/members/bio/3130/index.html">Learn More</a></p></p></div></div></div></div></div><!-- /.layout --></div></div><div class="bg-none section"><div class="row"><div class="layout"><div class="accordion" data-accordion="" id="accordion-2--1617265845"><div class="accordion-item"><h2><button aria-controls="panel-2--1617265845-1" class="accordion-title" id="panel-2--1617265845-1-heading"><span class="accordion-label has-content">Hunch #19: Can bacteria influence breast cancer progression and metastasis patterns? (2019)</span><span aria-hidden="true" class="accordion-icon"></span></button></h2></div><div aria-labelledby="panel-2--1617265845-1-heading" class="accordion-content" data-tab-content="" id="panel-2--1617265845-1" role="region"><p><a href="../../../about/members/bio/2983/index.html">Anna Maria Storniolo, MD</a><br/><br/>There are bacteria of all types everywhere in our bodies. Bacteria were originally thought to primarily inhabit our gut and aid in digestion. They are now shown to be present in different parts of the body, including the breast, and research has determined that the type of bacteria throughout our body depends on our ethnicity.<br/><br/>These observations raise questions about whether variations in types of bacteria in the breast might influence breast cancer initiation, progression and metastasis.<br/><br/>In this pilot study, the research team will use next-generation sequencing to identify bacteria that inhabit the breasts of healthy women, women with high-risk of developing breast cancer, and women diagnosed with breast cancer.<br/><br/>The results will be used to map the microbiome (bacterial population) in the breasts of women of different ancestry, living in different geographic locations. Ultimately, the goal is to identify bioactive compounds produced by bacteria that protect the breast from cancer and develop those compounds to treat and/or prevent metastatic progression of breast cancer.<br/><br/>The team will also look at whether the same ‘bad’ bacteria are found at sites of metastatic breast cancer and whether pre-treatment with antibiotics increases response to therapy.</p></div><div class="accordion-item"><h2><button aria-controls="panel-2--1617265845-2" class="accordion-title" id="panel-2--1617265845-2-heading"><span class="accordion-label has-content">Hunch #18: The impact of muscle on treatment response in women with metastatic ER positive breast cancer (2019)</span><span aria-hidden="true" class="accordion-icon"></span></button></h2></div><div aria-labelledby="panel-2--1617265845-2-heading" class="accordion-content" data-tab-content="" id="panel-2--1617265845-2" role="region"><a href="../../../about/members/bio/22023/index.html">Tarah Ballinger, MD</a><br/><br/>The majority of breast cancer deaths result from estrogen receptor (ER) positive, metastatic breast cancer (MBC), despite targeted therapies and treatment advances. Acknowledging that treatment affects a whole person rather than just a tumor, researchers have tried to determine how a woman’s body composition might contribute to her response to treatment.<br/><br/>These investigations have been limited, as weight-based measures alone do not tell the full story about a woman’s body, and women with the same weight or BMI can have very different amounts of muscle or fat.<br/><br/>This research team has a hunch that the amount of muscle in a woman’s body contributes to treatment outcome. Muscle is a large, active organ that influences the physical function, quality of life, metabolism, and inflammatory profile in the body. However, muscle has been understudied in women with MBC, and its impact has never been evaluated in those with ER positive metastatic disease.<br/><br/>To investigate this question, these researchers hope to analyze CT scans of women with ER positive MBC receiving aromatase inhibitors (the most commonly prescribed drug in breast cancer) to uncover any correlations between body composition and important treatment outcomes, including survival, quality of life, pain, and fatigue.<br/><br/>Results will help clinicians optimize drug dosing and potentially explain why effective drugs stop working for some patients. The long-term goal of this project is to provide recommendations for interventions that could positively impact treatment outcomes for women with ER positive metastatic breast cancer, such as state-of-the-art personalized resistance training programs and innovative non-exertional approaches to muscle development.</div><div class="accordion-item"><h2><button aria-controls="panel-2--1617265845-3" class="accordion-title" id="panel-2--1617265845-3-heading"><span class="accordion-label has-content">Hunch #17: Evaluation of SMIC1007 in treatment of metastatic breast cancers (2019)</span><span aria-hidden="true" class="accordion-icon"></span></button></h2></div><div aria-labelledby="panel-2--1617265845-3-heading" class="accordion-content" data-tab-content="" id="panel-2--1617265845-3" role="region"><p><a href="../../../about/members/bio/23805/index.html">Anita Bellail, PhD</a> and <a href="../../../about/members/bio/23404/index.html">Chunhai Hao, MD, PhD</a><br/><br/>The researchers proposing this hunch focus their work on determining what drives metastatic breast cancer and developing new therapies to combat it. They were the first to identify that a particular protein (called SUMO1) drives cancer growth and have developed a potent inhibitor (SMIC1007) that turns off this protein.<br/><br/>In cell culture, SMIC1007 inhibits the growth of multiple cancers including breast, colorectal, and lung. Hunch funding will allow this team to move SMIC1007 closer to the clinic, by testing it in two different animal models.<br/><br/>The first model uses a breast cancer cell line that metastasizes to the lungs. In the second model, they will use tumors from actual patients growing in mice. If successful, this hunch will support a new collaborative research team in generation of preliminary data necessary for the team to apply for the Department of Defense Breast Cancer Research Program and/or NCI drug development grants.<br/><br/>The ultimate goal of this project is to launch clinical trials of SMIC1007 treatment of metastatic breast cancers within five years.</p></div><div class="accordion-item"><h2><button aria-controls="panel-2--1617265845-4" class="accordion-title" id="panel-2--1617265845-4-heading"><span class="accordion-label has-content">Hunch #16: Correlative studies on a phase I trial of Gedatolisib Plus PTK7-ADC in metastatic triple negative breast cancer (2018)</span><span aria-hidden="true" class="accordion-icon"></span></button></h2></div><div aria-labelledby="panel-2--1617265845-4-heading" class="accordion-content" data-tab-content="" id="panel-2--1617265845-4" role="region"><p>Triple negative breast cancer (TNBC) is a devastating disease with poor outcomes and a lack of effective therapies. Typical treatment for TNBC usually entails administration of a variety of chemotherapies given as single agents (one at a time) for as long as the tumors are kept at bay or are shrinking in size. Unfortunately, single-agent therapy is not always clinically effective.<br/><br/>Many TNBC patients progress through multiple drugs and eventually end up succumbing to the disease. We have come to learn that resistance to single-agent therapy is common due to these tumors activating compensatory pathways. Imagine the inside of a tumor cell like a complex electrical wiring diagram - when one node is shut down, the current will reroute.<br/><br/>Likewise, when a key survival pathway (known as the PI3K pathway) is shut down by a drug, these tumors can rapidly reroute, activating another pathway (known as the Wnt pathway) that promotes tumor growth and survival. Targeting both of these is comparable to a game of whack-a-mole. Through extensive preclinical experimental testing, however, we have demonstrated the potential of two therapeutics, Gedatolisib and PTK7-ADC, for targeting both the PI3K pathway and the Wnt pathway simultaneously.<br/><br/>This year, we initiated a Phase 1 clinical trial combining Gedatolisib and PTK7-ADC for patients with metastatic triple negative breast cancer. The endpoints of this trial are to determine the safety of the combination and to observe early signals of clinical efficacy as determined by tumor response rate and patient survival. So far, eight patients have received the trial treatment drugs and five more are expected to join shortly.<br/><br/>However, the story does not end there. 100 Voices of Hope has continued to support this important effort, through choosing to fund this year's Hunch #16. This hunch will allow us to analyze all the data that comes back from the clinical trial. This will help us better understand the biology of which tumors respond to the new treatment and why some tumors can resist it.<br/><br/>The primary outcome of this hunch is to use this data to support a larger Phase 2 trial of the combination and advance its clinical development. Our long-term goal is to provide a new FDA-approved cutting-edge treatment for metastatic NBC patients.<br/><br/>The preclinical trial data to support the initiation of this trial were made possible by 100 Voices of Hope’s funded Hunch #4. <br/><br/>With help from your seed funding, our researchers recently received a National Cancer Institute grant to even further expand this project.</p></div><div class="accordion-item"><h2><button aria-controls="panel-2--1617265845-5" class="accordion-title" id="panel-2--1617265845-5-heading"><span class="accordion-label has-content">Hunch #15: Identification of “Tumor Compaction Factor X” in a Bone Microenvironment for Preventing Bone Metastasis from Breast Cancer (2018)</span><span aria-hidden="true" class="accordion-icon"></span></button></h2></div><div aria-labelledby="panel-2--1617265845-5-heading" class="accordion-content" data-tab-content="" id="panel-2--1617265845-5" role="region"><p><a href="../../../about/members/bio/3984/index.html">Hiroki Yokota, PhD</a><br/><br/>The researchers leading this pilot project expect it to open a new avenue to prevent metastatic breast cancer.<br/><br/>Bone is a common site for breast cancer to move and is often the first site where a recurrence of breast cancer is identified. In addition to being common, bone metastasis often causes great pain for patients, reducing their quality of life.<br/><br/>This hunch hopes to answer the questions:</p><ul><li>Why does breast cancer frequently metastasize to bone?</li><li>Does bone emit a special chemical signal that attracts breast cancer cells?</li><li>And can we block this signal and protect bone?</li></ul><p>Our researchers recently conducted real-time filming of bone-tumor interactions, which show osteocytes, the most abundant type of bone cells, interact with and cling to breast cancer cells like a magnet. This attraction seems to be induced by an unknown secretory protein factor from the osteocytes.<br/><br/>In this newly funded project, our researchers will work to identify the chemical and biological nature of the protein the osteocytes are releasing through mass spectrometry. Once the protein is determined, we should be able to explain why breast cancers tend to hone in on bone.<br/><br/>This knowledge could be used to develop novel treatments for preventing bone metastasis and could significantly improve the efficiency of drug delivery for breast cancer patients.</p></div><div class="accordion-item"><h2><button aria-controls="panel-2--1617265845-6" class="accordion-title" id="panel-2--1617265845-6-heading"><span class="accordion-label has-content">Hunch #14: A Novel Epigenetic-PARP Inhibitor Combination to Inhibit Metastasis in Triple Negative Breast Cancer (2018)</span><span aria-hidden="true" class="accordion-icon"></span></button></h2></div><div aria-labelledby="panel-2--1617265845-6-heading" class="accordion-content" data-tab-content="" id="panel-2--1617265845-6" role="region"><p><a href="../../../about/members/bio/22423/index.html">Richard Carpenter, PhD</a> and <a href="../../../about/members/bio/1160/index.html">Kenneth Nephew, PhD</a><br/><br/>This hunch brings together two unique areas of research, epigenetics and PARP inhibitors, to improve therapies available for triple negative breast cancer (TNBC), a highly aggressive form of breast cancer that occurs in 15 percent to 25 percent of patients.<br/><br/>Epigenetics is the process by which cells control their function. Epigenetics describes the cellular proteins that tell genes what to do, where to do it, and when to do it. Cancer cells take advantage of this process and turn on genes in cells that stimulate growth, while turning off the genes that regulate and control growth.<br/><br/>If we understand the process of epigenetics, we could utilize it in treatment, turning off what cancer has turned on. The other area of research this hunch encompasses is PARP inhibitors, a new class of drugs that treat cancer through accelerating DNA repair.<br/><br/>These treatments have already proved to be very effective and provide less side effects for the women being treated; however, they are only effective in women with a BRCA genetic mutation.<br/><br/>The goal of this hunch is to use the combination of epigenetics and PARP inhibitors to treat mice with breast cancer, and determine if this combination will be a viable treatment option for women with TNBC who do not have the BRCA mutation.</p></div></div></div><!-- /.layout --></div></div><div class="breakout bg-crimson bg-dark section"><div class="row"><div class="layout"><div class="callout"><div class="content"><p>Better results for patients are possible through our exploration of the genetics that drive tumors, what makes tumors more susceptible to treatment, and devising therapies to defeat breast cancer while avoiding toxic side effects.</p></div></div></div><!-- /.layout --></div></div><div class="breakout bg-gray section"><div class="row"><div class="layout"><div class="text"><h3>100 Voices of Hope “hunch” headlines</h3><ul><li><a href="#">'Whac-a-Mole' clinical trial participant experiences remission of Stage 4 triple negative breast cancer</a> (November 2021)</li><li><a href="#">IU School of Medicine researchers discover small molecule degrader as potential anticancer drug</a> (October 2021)</li><li><a href="#">Cancer center researchers part of a collaborative $12.4 million SPORE grant from National Cancer Institute</a> (
September 2021_</li><li><a href="#">IU School of Medicine researchers discover game-changer combination drug for triple negative breast cancer</a> (February 2021)</li><li><a href="#">IU cancer center researchers discover how breast cancer cells hide from immune attack</a> (January 2021)</li></ul></div></div><!-- /.layout --></div></div><div class="bg-none section"><div class="row"><div class="layout"><div class="accordion" data-accordion="" id="accordion-3--1617265845"><div class="accordion-item"><h3><button aria-controls="panel-3--1617265845-1" class="accordion-title" id="panel-3--1617265845-1-heading"><span class="accordion-label has-content">Hunch #13: Biology of Breast Cancer Health Disparity (2017)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-3--1617265845-1-heading" class="accordion-content" data-tab-content="" id="panel-3--1617265845-1" role="region"><p>The goal of this hunch is to answer the critical biological question of why breast cancer presents differently among different groups of women.<br/><br/>Although breast cancer is less common among African American women when compared to Caucasian women, the outcomes for African American women are generally poor, even after considering socioeconomic and healthcare access issues.<br/><br/>By contrast, Hispanic women develop less aggressive breast cancers and have better outcomes. Through understanding the biologic differences between normal breast tissues of different ethnic groups, we may be able to decipher reasons for this health disparity.<br/><br/>This hunch will allow a group of researchers to obtain sufficient preliminary results to develop a multi-million dollar project proposal that will be submitted to the National Cancer Institute by early 2018. IU is the only place with resources to address these questions because of the availability of more than 5,000 normal breast tissue samples through the <a href="https://komentissuebank.iu.edu/">Komen Tissue Bank</a>.<br/><br/>The goal of this project is to identify the genetic factors that make cancer more or less aggressive. This could help to better characterize tumors in all women and lead to improved treatment of breast cancer in the future.</p></div><div class="accordion-item"><h3><button aria-controls="panel-3--1617265845-2" class="accordion-title" id="panel-3--1617265845-2-heading"><span class="accordion-label has-content">Hunch #12: A Novel Approach to Discover Drug Resistance Genes in Metastasized Breast Cancer Cells (2017)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-3--1617265845-2-heading" class="accordion-content" data-tab-content="" id="panel-3--1617265845-2" role="region"><p><em>Funded in memory of Carrie Glasscock West</em><br/><br/><a href="../../../about/members/bio/10001/index.html">Tao Lu, PhD</a> and Lang Li, PhD<br/><br/>We hypothesize that high expression of some key proteins leads to drug resistance in metastasized breast cancer. Recently, our lab has developed an extremely innovative technique called validation-based insertional mutagenesis (VBIM), for novel gene discovery.<br/><br/>This project uses the VBIM technique to identify key proteins that lead to chemotherapy resistance in metastasized breast cancer cells. The researchers will analyze a panel of clinically-used drugs with different cell killing mechanisms to perform the experiments.<br/><br/>Overall, this unique and comprehensive approach could give physicians the important information they need to design more rational and precise therapies with greater effectiveness for breast cancer patients.</p></div><div class="accordion-item"><h3><button aria-controls="panel-3--1617265845-3" class="accordion-title" id="panel-3--1617265845-3-heading"><span class="accordion-label has-content">Hunch #11: In memory of Anne Abernethy (2016)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-3--1617265845-3-heading" class="accordion-content" data-tab-content="" id="panel-3--1617265845-3" role="region"><p>Milan Radovich, PhD<br/><br/>Dr. Radovich and his team plan to test two FDA-approved drugs in mice with triple negative tumors that have shown great potential for being an effective combination.<br/><br/>If they receive positive results, this hunch would be used to support the launch of Phase I/II clinical trials. Their hope is that this combination will provide a new “precision medicine” based drug combination for triple negative breast cancer.</p></div><div class="accordion-item"><h3><button aria-controls="panel-3--1617265845-4" class="accordion-title" id="panel-3--1617265845-4-heading"><span class="accordion-label has-content">Hunch #10: In memory of Mary Corbett (2016)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-3--1617265845-4-heading" class="accordion-content" data-tab-content="" id="panel-3--1617265845-4" role="region"><p>Hunch #10 is spearheaded by Drs. Jian-Ting Zhang, Jing-Yuan Lui, and Hal Broxmeyer. It focuses on triple negative breast cancer and immunotherapy, a very promising area in cancer research where drugs are used to train our own bodies to attack aggressive tumors.<br/><br/>The team is working on finding an alternative to a very effective immunotherapy drug—pembrolizumab—that Jimmy Carter received recently. Finding an alternative is key because the cost of pembrolizumab exceeds $1 million a year.<br/><br/>Dr. Zhang and his team will screen a library of FDA-approved drugs to look for matches, with the goal of identifying an alternative that is easy to make and has already been demonstrated as safe in humans.</p></div><div class="accordion-item"><h3><button aria-controls="panel-3--1617265845-5" class="accordion-title" id="panel-3--1617265845-5-heading"><span class="accordion-label has-content">Hunch #9: Create a microfluidic device that senses metastatic cancer cells in the bloodstream (2015)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-3--1617265845-5-heading" class="accordion-content" data-tab-content="" id="panel-3--1617265845-5" role="region"><p><a href="../../../about/members/bio/3984/index.html">Hiroki Yokota. PhD</a>, and <a href="../../../about/members/bio/3235/index.html">David Agarwal, MD</a><br/><br/>The winning hunch for 2015 is innovative in two ways. It is the first collaborative project we’ve funded with a team of Purdue biomedical engineers. Second, this hunch applies to all types of metastasis and focuses on developing a microfluid device that can circulate in the bloodstream and destroy metastatic cancer cells as they migrate.<br/><br/>The team of researchers includes Dr. Hiroki Yokota, biomedical engineer; Dr. Likhun Zhu, mechanical engineer; Dr. Sungsoo Na, biomedical engineer; Dr. Jong Eun Ryu, mechanical engineer; and Dr. Mangilal Agarwal, Associate Director of Research Development. Dr. Yokota also works with Dr. Hari Nakshatri on Hunch #8.<br/><br/>The purpose of the project is to create a microfluidic device that senses metastatic cancer cells in the bloodstream and destroys them. Specifically, the device will detect cell wall stiffness, which is different in cancer cells versus normal cells.<br/><br/>This is proof-of-concept funding, meaning that we are funding the idea at its beginning stages—the hardest time to attract support. As we move forward in cancer research, more collaboration between the physical sciences including engineering and the biological sciences including chemistry is pivotal.<br/><br/>Both sides offer unique perspectives in how we can treat and stop metastasis, which is the primary reason people lose their lives to cancer.</p></div><div class="accordion-item"><h3><button aria-controls="panel-3--1617265845-6" class="accordion-title" id="panel-3--1617265845-6-heading"><span class="accordion-label has-content">Hunch #8: Validating Anti-Cancer and Bone-Strengthening Effects of Guanabenz (2014)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-3--1617265845-6-heading" class="accordion-content" data-tab-content="" id="panel-3--1617265845-6" role="region">The drug guanabenz has been shown to kill breast cancer cells and stop the spread of breast cancer cells to bone in the laboratory. However, persistent bone pain experienced by patients with bone metastasis is largely due to bone loss. Guanabenz is also shown to prevent bone degradation and promote new bone formation, which will help to alleviate pain.<br/><br/>This hunch proposes to validate guanabenz’s anti-cancer and bone-strengthening effects in a formalized laboratory study. The team’s goal is to develop data to initiate clinical studies with this drug to demonstrate prevention and treatment of bone metastases and to rebuild bones damaged by cancer.</div></div></div><!-- /.layout --></div></div><div class="breakout bg-crimson bg-dark section"><div class="row"><div class="layout"><div class="callout"><div class="content"><p>New discoveries start with your gifts. This vital work means so much to breast cancer patients, their families, their friends, and the communities they enrich.</p></div></div></div><!-- /.layout --></div></div><div class="collapsed bg-none section"><div class="row"><div class="layout"><div class="accordion" data-accordion="" id="accordion-4--1617265845"><div class="accordion-item"><h3><button aria-controls="panel-4--1617265845-1" class="accordion-title" id="panel-4--1617265845-1-heading"><span class="accordion-label has-content">Hunch #7: How Do Cancer Cells Turn Off Metastasis Suppressor Genes? (2014)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-4--1617265845-1-heading" class="accordion-content" data-tab-content="" id="panel-4--1617265845-1" role="region"><p>The investigators are studying a group of metastasis suppressor genes (MSGs) thought to play an important role in preventing the development of metastases.<br/><br/>In experimental models, turning off the MSGs increases the frequency and size of metastasis, and human tumors that have turned off the MSGs have a worse prognosis. Unlike some other cancer genes, the MSGs are not “mutated,” they are just turned off.  <br/><br/>The main question this research is trying to answer is: How do cancer cells turn off MSGs? Using data from the Cancer Genome Atlas, an NCI-sponsored project including genomic data from almost a 1,000 breast cancer patients, the team will identify and analyze lncRNAs associated with metastasis.</p></div><div class="accordion-item"><h3><button aria-controls="panel-4--1617265845-2" class="accordion-title" id="panel-4--1617265845-2-heading"><span class="accordion-label has-content">Hunch #6: IPR1110 as a Chemotherapeutic Agent (2013)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-4--1617265845-2-heading" class="accordion-content" data-tab-content="" id="panel-4--1617265845-2" role="region"><p><a href="../../../about/members/bio/3531/index.html">Samy Meroueh, PhD</a><br/><br/>Dr. Meroueh’s lab is working to chemically link IPR1110 to a chemotherapeutic so that when the molecule attaches to uPAR it delivers the drug to malignant cells. The main question his research is trying to answer is whether IPR1110 can attach to uPAR successfully and deliver the chemotherapeutic to destroy malignant cells while excluding healthy cells.<br/><br/>Dr. Meroueh anticipates that the molecule IPR1110 may also act as a stand-alone agent for the treatment of metastasis. His recent data verifies that IPR1110 can be used as both a homing agent to deliver a chemotherapeutic and may be useful as a therapeutic agent.</p></div><div class="accordion-item"><h3><button aria-controls="panel-4--1617265845-3" class="accordion-title" id="panel-4--1617265845-3-heading"><span class="accordion-label has-content">Hunch #5 (2012)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-4--1617265845-3-heading" class="accordion-content" data-tab-content="" id="panel-4--1617265845-3" role="region"><p>Dr. Milan Radovich sequenced the genomes of 135 patients with triple negative tumors being treated with a new drug combination and presented his finding at the 2014 annual meeting of the American Society of Clinical Oncology (ASCO).  <br/><br/>Those results demonstrated a druggable pathway and RNA biomarkers that mediate chemotherapy resistance in triple negative tumors. Dr. Radovich is currently sequencing the plasma from the trial which allows for sensitive detection of treatment response and relapse in patients.<br/><br/>In collaboration with industry, Dr. Radovich has early access to a diagnostic tool that will allow his lab to detect circulating tumor DNA with an extremely high sensitivity. They are also in the early phases of developing a new analysis method for circulating RNA biomarkers in anticipation of submitting an NIH proposal specifically for RNA biomarkers for early cancer detection.<br/><br/>This work has identified novel mechanisms of why triple-negative breast cancers can become re-sistant to chemotherapy in newly diagnosed patients. Patients who have residual tumors after chemotherapy have a high recurrence rate. Further, the data is informing the laboratory of new therapeutic interventions for those patients who develop resistance.</p></div><div class="accordion-item"><h3><button aria-controls="panel-4--1617265845-4" class="accordion-title" id="panel-4--1617265845-4-heading"><span class="accordion-label has-content">Hunch #4 (2011)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-4--1617265845-4-heading" class="accordion-content" data-tab-content="" id="panel-4--1617265845-4" role="region"><p>Dr. Milan Radovich is in the final phase of completing the mouse studies in collaboration with industry using a novel drug combination for triple-negative breast cancer.<br/><br/>The two-drug combination has been so successful that treatment to mice had to stop so that researchers would have enough residual tumor to analyze. A final anti-tumor efficacy study of the drug combination is being tested in mice with implanted human tumors to see if the response to treatment remains effective.<br/><br/>Dr. Radovich has been invited to submit an Investigator Initiated Trial grant request with the hopes of opening a Phase I trial in metastatic triple negative breast cancer within six months.</p><ul><li>Dr. Radovich’s lab found a new drug combination that significantly reduced triple negative breast cancer tumors in animals.  In collaboration with industry, this 100 VOH-funded research will be moving into a clinical trial within six months.</li><li>He presented research at the Annual San Antonio Breast Cancer Symposium in December 2013.</li></ul></div><div class="accordion-item"><h3><button aria-controls="panel-4--1617265845-5" class="accordion-title" id="panel-4--1617265845-5-heading"><span class="accordion-label has-content">Hunch #3: Biomarker ESPR1 and ER-Positive Breast Cancer (2010)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-4--1617265845-5-heading" class="accordion-content" data-tab-content="" id="panel-4--1617265845-5" role="region"><p><span style="font-weight: 400;">The goal of this project is to determine genes that are involved in the late recurrence of breast cancer, particularly estrogen receptor (ER) positive breast cancer. Breast tissue taken at the time of diagnosis is being compared with tissue from women who are taking hormonal therapies at five and 10 years out to learn which genes are being expressed.<br/><br/>The first part of the research focuses on the biomarker ESPR1 and its role in endocrine resistance. Endocrine therapy is an important part of ER-positive breast cancer treatment; patients sometimes develop resistance leading to late recurrence. It has been found that in patients with endocrine resistance, there is a higher expression of ESRP1, resulting in poor outcomes. <br/><br/>The second part of the research involves a genetic analysis of tumors from 2,000 patients with ER-positive breast cancer. This provides a very thorough breakdown of genetic differences between tumor types. Knowing the gene pathways in tumors that lead to late recurrence will give investigators a picture of genes that can be targeted for therapeutics.</span><span style="font-weight: 400;"></span></p></div><div class="accordion-item"><h3><button aria-controls="panel-4--1617265845-6" class="accordion-title" id="panel-4--1617265845-6-heading"><span class="accordion-label has-content">Hunches #1 and #2: Improving Cardiac Function in Breast Cancer Patients (2009)</span><span aria-hidden="true" class="accordion-icon"></span></button></h3></div><div aria-labelledby="panel-4--1617265845-6-heading" class="accordion-content" data-tab-content="" id="panel-4--1617265845-6" role="region"><p><a href="../../../about/members/bio/1111/index.html">Hari Nakshatri, PhD</a><br/><br/>Dr. Nakshatri identified a potential biomarker for recurrent breast cancer in circulating blood; he patented his biomarker and secured a $400,000 National Cancer Institute-funded grant to expand the project.</p><p>While this project has been successfully completed, his research continues and is focusing on how to improve cardiac function in breast cancer patients. He is seeking grant funding.</p><ul><li>Dr. Nakshatri’s research and 100 VOH funding resulted in a $400,000 National Cancer Institute-funded grant.</li><li>His work was published in both Breast Cancer Research and Cancer Research, the most highly cited cancer research journal in the world.</li></ul></div></div></div><!-- /.layout --></div></div>
</header><main><div class="content-top"><div class="section breadcrumbs"><div class="row"><div class="layout"><ul itemscope="itemscope" itemtype="http://schema.org/BreadcrumbList"><li itemprop="itemListElement" itemscope="itemscope" itemtype="http://schema.org/ListItem"><a href="../../../index.html" itemprop="item"><span itemprop="name">Home</span></a><meta content="1" itemprop="position"/></li><li itemprop="itemListElement" itemscope="itemscope" itemtype="http://schema.org/ListItem"><a href="../../index.html" itemprop="item"><span itemprop="name">Giving</span></a><meta content="2" itemprop="position"/></li><li itemprop="itemListElement" itemscope="itemscope" itemtype="http://schema.org/ListItem"><a href="../index.html" itemprop="item"><span itemprop="name">Donor Highlights</span></a><meta content="3" itemprop="position"/></li><li itemprop="itemListElement" itemscope="itemscope" itemtype="http://schema.org/ListItem"><a href="index.html" itemprop="item"><span itemprop="name">Indiana Elks Association</span></a><meta content="4" itemprop="position"/></li><li class="current" itemprop="itemListElement" itemscope="itemscope" itemtype="http://schema.org/ListItem"><span itemprop="name">Report to the Indiana Elks 2021</span><meta content="5" itemprop="position"/></li></ul></div></div></div><div class="section page-title bg-none"><div class="row"><div class="layout"><h1>Report to the Indiana Elks 2021</h1></div></div></div></div><div id="main-content"><div class="bg-secondary bg-dark section" id="content"><div class="row"><div class="layout"><h2 class="section-title">Indiana: Home to Innovative Cancer Research and Care </h2><div class="text"><p><strong>INDIANA ELKS</strong> and <strong>IU SCHOOL OF MEDICINE</strong></p></div><figure class="media image" itemscope="itemscope" itemtype="http://schema.org/ImageObject"><img alt="" src="../../../images/people/brian_stokes-768x768.jpg"/></figure></div><!-- /.layout --></div></div><div class="bg-gray section"><div class="row"><div class="layout"><div class="text"><h3>Research funded by the Indiana Elks benefits patients in Indiana and beyond </h3><p><strong>REPORT TO THE INDIANA ELKS 2021</strong></p></div></div><!-- /.layout --></div></div><div class="bg-none section"><div class="row"><div class="layout"><div class="text"><h3>IU Simon Comprehensive Cancer Center delivers treatment close to home</h3><p>Though he is a native of South Bend, Indiana, Brian Stokes lived in several states over the years. In 2015, he and his husband, Lance Gustin, moved back to South Bend from Chicago and began to settle in.  <br/>   <br/>“I’ve always been drawn back to Indiana,” Brian said. “My family is here, and it’s just home.” <br/> <br/>Lance and Brian soon found themselves members of the Indiana Elks: Lance became an Elk in 2015 and Brian in 2019. Over the years, they have learned about the incredible impact the Elks make on cancer research at both Indiana University and Purdue University. They have witnessed firsthand the hard work Elks do to raise funds to help eradicate cancer in Indiana and beyond. And, they have felt fortunate to be a part of something so special in their home state. They never imagined how critically important these efforts would become to them personally.</p></div><figure class="media image" itemscope="itemscope" itemtype="http://schema.org/ImageObject"><img alt="" src="../../../images/people/lance_and_brian-768x512.jpg"/><figcaption itemprop="caption"><span class="caption-text">Lance (left) and Brian</span></figcaption></figure><div class="text"><p>In
September 2020, Brian saw a doctor, hoping to get some answers about the fatigue and stomach issues he had been experiencing for a while. He had been attributing his ailments to stress related to work and the COVID-19 pandemic. His doctor ordered bloodwork just to make sure Brian had not developed irritable bowel syndrome. <br/> <br/>The following morning, Brian’s doctor called and advised him to go directly to the emergency room. His hemoglobin was dangerously low, and he needed a blood transfusion. The hospital care team determined that Brian was bleeding internally, but they weren’t sure of the source. A CT scan and a colonoscopy revealed terrible news: Brian had Stage III colon cancer. <br/> <br/>“The next thing we knew, there was a flurry of doctors coming in and out of the room, talking about surgeries, life-changing alterations for Brian, treatments, outcomes... the list goes on,” Lance said.  <br/> <br/>After hearing all the overwhelming information from the physicians at their local hospital, Lance and Brian said they wanted a second opinion from someone at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center.  <br/> <br/>“We explained that it wasn’t because we didn’t trust them, but that we are Elks and have a strong affiliation with IU though our philanthropic work,” Lance said. <br/> <br/>Within hours of reaching out to IU, Lance got a call from former director of the IU Simon Comprehensive Cancer Center, Patrick Loehrer, MD. Loehrer asked for permission to access Brian’s medical information and present it the next day to the cancer center’s “Tumor Board,” where various medical experts comprehensively review the patient’s situation, including X-rays and scans, pathology report and other medical records. The group—which typically includes surgeons, medical oncologists, radiation oncologists, pathologists and other specialists—makes a recommendation for the patient’s treatment plan.     <br/>  <br/>Loehrer arranged for Brian to see cancer center surgeon Bryan Holcomb, MD, just one week after the initial diagnosis. Holcomb assured Brian that the IU team agreed with the treatment plan his local hospital had suggested and recommended Brian undergo chemotherapy and radiation back in South Bend, lifting the burden of travel. He assured Brian that the IU team would monitor his progress, and he would have periodic follow-up appointments in Indianapolis. Holcomb also said he would like Brian to consider participating in an IU clinical trial once his cancer was under control.</p></div><figure class="media image" itemscope="itemscope" itemtype="http://schema.org/ImageObject"><img alt="" src="../../../images/people/no_one_fights_alone-768x512.jpg"/></figure><div class="text"><p>On November 25, 2020, after five weeks of chemotherapy and 36 rounds of radiation, Brian received great news: his tumor was no longer detectable. <br/> <br/>“Brian got to ring that bell,” Lance said, referring to the tradition of ringing a bell to signify the conclusion of cancer treatment. “And we got to have a great Thanksgiving.” <br/> <br/>After spending the holidays celebrating, Brian enrolled in an IU clinical trial to study the effects of a potential immune-boosting drug that may help prevent his cancer from recurring.  <br/> <br/>Brian and Lance are relieved to have access to top-notch care, informed by research, right in their own backyard. They are grateful to their fellow Indiana Elks for the time and effort they put toward advancing cancer research, right here at home.</p></div></div><!-- /.layout --></div></div><div class="breakout bg-crimson bg-dark section"><div class="row"><div class="layout"><div class="float-left one-third"><figure class="media image" itemscope="itemscope" itemtype="http://schema.org/ImageObject"><img alt="" src="../../../images/people/anita_turk-768x768.jpg"/></figure></div><div class="float-right two-thirds"><div class="text"><h3>Anita Turk, MD</h3><p>Clinical trials allow doctors to test new drugs and drug combinations to improve the standard of care. The IU clinical trial in which Brian is participating is directed by Anita Turk, MD, an assistant professor of clinical medicine at IU School of Medicine and associate member of the Experimental and Developmental Therapeutics research program at the IU Simon Comprehensive Cancer Center.  <br/> <br/>The trial seeks to determine if giving immunotherapy drugs after cancer patients complete chemotherapy and radiation decreases the risk of recurrence by triggering the immune system to fight any residual cancer. Brian requires six cycles of treatment, once every four weeks. After this is complete, Brian will have long-term follow-up with Turk and the clinical trial team for up to five years. <br/> <br/>“People who participate in clinical trials are unsung heroes,” Turk said. “They are a critical component of helping us improve the care we deliver moving forward. If patients stop enrolling in clinical trials, progress stops.”</p></div></div></div><!-- /.layout --></div></div>