Pancreatic Cancer

HALTING PANCREATIC CANCER goes beyond finding treatments. It requires a comprehensive approach: non-invasive tests to catch it early; molecular studies to understand how it evolves; and using those insights to create targeted therapies. That’s how we will improve a survival rate that remains stubbornly low—around 10 percent overall and closer to three percent for those with metastatic disease.

Halting this disease also demands a team approach–the kind we use at Indiana University School of Medicine.

More than 20 faculty members at IU Melvin and Bren Simon Comprehensive Cancer Center—surgeons, oncologists, laboratory scientists and biostatisticians—make up a Pancreatic Cancer Challenges and Solutions Working Group dedicated to seeking solutions. They have created nuanced models that mimic the environment around a tumor, and those models have helped identify potential drug targets.

The group reached an exciting milestone this year.

In October, the team applied for a Specialized Program of Research Excellence (SPORE) grant from the National Institutes of Health. Only six institutions nationwide have earned that distinction, which is reserved for programs that show stellar collaboration and whose ideas move seamlessly between the lab bench and the patient’s bedside. If awarded, the IU Simon Comprehensive Cancer Center would lead the only pancreatic cancer SPORE in the Midwest, joining an elite group that includes the Mayo Clinic, Memorial Sloan-Kettering, and M.D. Anderson.

Your generous support helps us assemble a top-flight team, equip them with the latest tools, and support bold ideas early. Together, we are making IU a national leader in pancreatic cancer research and treatment. And above all, we’re making discoveries with the potential to save lives. Here’s a glimpse at where we want to go next.

Pancreatic cancer tumors and their environments are complex and harsh. So, we’ve developed state-of-the-art models to mimic those conditions–and patients play an invaluable role.

IU Health surgeons perform more pancreatic cancer surgeries than any other team in the nation. This high volume of surgeries yields diverse tumor samples that are stored in a tissue bank researchers can use in 3-D models. After surgeons remove tumors, patients can donate portions of their tumor tissue to a tissue bank at IU School of Medicine. These gifts are crucial and can be sources for cell-based studies or to grow and test microtumors–a process we developed and now share with other institutions.

Tumor samples can teach us about pancreatic cancer’s deadly mechanisms and stubborn defenses. They could also be ideal proving grounds for drugs and combination therapies. IU has already used the tissue to explore why pancreatic patients often develop severe clotting issues. Likewise, from these modest amounts of tissue, we hope to uncover insights that improve care.

Our faculty also want to leverage the power of big data to make crucial discoveries and speed up identifying new treatment targets and molecules.

In the past year, JING SU, PHD, and ASHIQ MASOOD, MD, have joined the working group and brought a distinct expertise to the team. Su, an assistant professor of biostatistics and health data science, can mine publicly available data to identify potential targets and new molecules. Meanwhile, Masood, who leads IU’s gastroenterology program, is adept at using bioinformatics to sequence cells from pancreatic cancer tumors.

As part of our SPORE application, we intend to build a big data core that would support ongoing research, new projects focused on detection of early-stage pancreatic cancer and career development for young faculty intent on studying the disease.

Pancreatic cancer has developed ways to withstand the stress created by chemotherapy. We’re figuring out how to strip it of that protection.

Traditional therapy creates a low-oxygen environment and makes it hard for cancer cells to produce the energy they need to survive. MARK KELLEY, PHD, and longtime collaborator MELISSA L. FISHEL, PHD, have developed a drug targeting a pathway that helps cancer cells repair their own DNA that’s been damaged by chemotherapy. Recently, Kelley and Fishel found that a relatively modest dose of the drug suppresses the helper cells—damaged immune cells that have become cancerous. The drug can kill cancer.

Now, they need to untangle why it’s happening. The duo wants to run a clinical trial where patients receive their drug during a two-week period before surgery. Then, they’ll compare biopsies from before and after therapy. Ideally, the data will help them design a combination therapy.

Almost one-third of patients with pancreatic cancer die from muscle wasting–a condition called cachexia–but we lack biomarkers to catch this early on and treatments to stop it. We’re trying to change that.

In the past year, TERESA ZIMMERS, PHD, and other collaborators from across the country identified several pathways that power cachexia. In many cases, drugs already approved to treat other conditions could be applicable for cachexia. Zimmers recently moved to Oregon Health & Science University but will continue working with the IU team on a project that aims to determine if these drugs can cut off cachexia pathways. Ideally, the clinical trial would enroll patients receiving chemotherapy who have not undergone surgery. The target for the clinical trial is a protein that helps regulate the immune system’s response to inflammation, but in cachexia, it spurs the breakdown of muscle and fat tissue.

Data from animal models show that blocking this protein reduces muscle loss, slows down tumor growth, and makes cancer more responsive to therapy. The trial—using an existing drug that combats severe arthritis—will look at safety and dosing. Researchers will also evaluate tumor samples to see whether chemotherapy is more effective.

There’s a chance it could be the first step toward developing a combination therapy that attacks pancreatic cancer and prevents cachexia.