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 new strategies for targeted therapies. That’s how we will improve a survival rate that remains stubbornly low—around 13 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 Melvin and Bren Simon Comprehensive Cancer Center.

Your generous support helps us assemble a world-class 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.

More than 90 laboratory scientists, oncologists, biostatisticians, and population scientists comprise the Pancreatic Cancer Challenges and Solutions Working Group, which is dedicated to seeking solutions. This working group is led by IU researchers Melissa Fishel, PhD, the Myles Brand Scholar in Cancer Research, and Purdue researcher Brittany Allen-Petersen, PhD. This dynamic team brings together researchers from IU, Purdue and Notre Dame—ensuring its multidisciplinary researchers can collaborate and move research advances quickly with clinical input from Ashiq Masood, MD, and Anita Turk, MD.

Over three decades, IU surgeon C. Max Schmidt, MD, PhD, and colleagues have made significant research contributions that have informed international treatment guidelines and help reduce the burden of pancreatic cancer worldwide.

Approaches and technologies developed at IU are focused on the early detection and prevention of pancreatic cancer in patients at high risk, as well as better defining which patients may benefit from pancreatic cancer surgery. Finding reliable markers of both cancer and of benignity (lesions than are not cancerous) are main areas of focus in Dr. Schmidt’s research in his Pancreatic Cyst and Cancer Early Detection Center.

Often pancreatic cancer is found late when few treatment options are available. Detecting pancreatic cancer early could be a game-changer for many patients. Thanks to the Evan and Sue Ann Werling Pancreatic Cancer Research Fund, IU researchers are exploring how a urine-based test could detect pancreatic cancer long before symptoms appear.

Tim Lautenschlaeger, MD, Dr. Turk and Dr. Schmidt have developed a urine test to detect circulating tumor DNA, or ctDNA, which is DNA released by cancer cells. While blood is most often used to detect ctDNA, researchers think urine would be more effective due to the larger sample volume, and it could allow for easy at-home testing. The group is collecting urine and blood samples from late-stage pancreatic cancer patients to study how well their test detects pancreatic cancer-related genetic mutations. They are then comparing the performance of their urine-based test with that of existing blood-based tests. Urine samples from early-stage pancreatic cancer patients are also being collected and compared to samples from healthy patients of similar age to determine the test’s ability to detect early-stage disease. Ultimately, they hope to create a simple pancreatic cancer screening method for those at risk of developing the disease.

Cancer cachexia – the loss of body weight and muscle mass – is a devasting syndrome that affects about 80% of pancreatic cancer patients, leading to decreased quality of life and ultimately higher mortality rates because patients with cachexia are too weak to be treated with chemotherapies. IU researchers are working together to discover new ways to address this devasting syndrome.

Researchers have identified a protein that may be a target for treating pancreatic cancer and the associated cachexia. Aneesha Dasgupta, PhD, Jason Doles, PhD, Chafiq Hamdouchi, PhD, and Dr. Turk received cancer center pilot funding to investigate how this protein affects cancer progression and to test new compounds that they shortlisted for successfully decreasing tumor burden and reducing muscle wasting.

Pilot projects like these are funded by donors like you. These projects allow researchers to gather meaningful initial data which allows them to then apply for significant external funding.

Building on their longtime collaborative work, Melissa Fishel, PhD, and Mark Kelley, PhD, are exploring new therapies that target the critical pathways pancreatic tumors use to survive. They received a highly competitive National Cancer Institute (NCI) grant to build on the advances made in their adjacent labs. They are investigating new therapy combinations and evaluating how well combination therapies overcome a cancer cell’s resistance—and ultimately moving the best therapies toward clinical trials.

Fishel also is exploring another new target in pancreatic cancer research. As part of the NCI’s Pancreatic Ductal Adenocarcinoma Stromal Reprogramming Consortium, Fishel and her colleagues hope to lessen or eliminate chemoresistance and drug-delivery barriers in pancreatic cancer treatment. She is working alongside investigators at University of Illinois- Urbana-Champaign and University of North Carolina-Chapel Hill.

Led by Dr. Masood, IU researchers have mapped pancreatic cancer tumor ecosystems using tissue from both the primary tumor, which is where cancer first starts to grow in the body, and metastatic disease, which is when cancer cells spread to different parts of the body beyond the primary tumor. This study uncovers notable differences between primary and metastatic pancreatic cancer, which could lead to new treatment strategies for the often-deadly disease.

Using tumor tissue from surgical resections of pancreatic cancer and disease that spread to the liver, pancreas and lymph nodes, Masood and his research team were able to study the varying "neighborhoods" of pancreatic cancer. 

Much of pancreatic cancer research has previously focused on the primary tumor, but understanding how the disease spreads is crucial to developing new treatments. Masood and the research team identified seven distinct spatial neighborhoods, or spatial ecotypes, in the primary tumor and metastases. Each neighborhood has a unique makeup of cells and gene activity.

IU and its health care partner Indiana University Health have one of the highest-volume pancreatic cancer programs in the country, with surgeons performing more pancreatic cancer surgeries than any other team in the nation. This makes IU uniquely positioned to yield diverse tumor samples that are stored in a tissue bank for cancer research.

After surgeons remove tumors, patients can donate portions of their tumor tissue to a tissue bank at IU. This tissue can then be used in research settings to explore various mechanisms of cell survival, drug resistance and novel therapies with the use of organoids and patient-derived tumors grown in mice called PDX or patient-derived xenografts. Already, more than 45 patients have contributed tissue samples to this PDX bank. These gifts are crucial for research and can be sources for cell-based studies or for growing and testing microtumors or organoids—a process we developed and now share with other institutions.

Additionally, researchers are working to establish organoids from fine-needle biopsies of patients with metastatic pancreatic cancer. This effort aims to expand our bank of patient samples since the majority of these patients do not have resectable tumors.

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. These modest amounts of tissue will help uncover insights that improve care.

In another research project, Doles, Dasgupta, and Joshua Huot, PhD, are using models developed from patient tumor samples to better understand and treat cachexia. By developing these new models, researchers hope to study pancreatic cancer and cachexia more effectively.