Pancreatic cancer is a complex condition to treat, as symptoms are often not apparent until the cancer has advanced to the point where it has spread beyond the pancreas. It is the third leading cause of cancer-related death in the United States, with patients succumbing to the disease within 6 months of diagnosis on average. But now, more than ever, patients with pancreatic cancer have good reason to be optimistic about their futures. In the past 10 years, knowledge about pancreatic cancer has increased dramatically, and we are at the frontier of promising new therapies to treat this disease.
The Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute includes world-class experts in gene discovery, functional genomics, chemical biology, computational biology, immunotherapy, and model system development, as well as individuals in clinical roles, including radiology, pathology, and clinical trials. This collaborative research environment has resulted in the creation of a pipeline for innovation in the areas of detection and treatment of pancreatic cancer, translating high impact research findings into potential new therapies for patients. One such innovation includes establishing one of the most sophisticated clinical trials programs for pancreatic cancer at any cancer center in the world, with the work of this group contributing to the first targeted drug approval for patients with pancreatic cancer. Dana-Farber also established a comprehensive early detection program for patients with inherited risk of pancreatic cancer, which is now the model for the rest of the country.
The DEKM Fund is currently supporting pancreatic cancer research in the Mancias lab at Dana-Farber. Led by Joseph Mancias, MD, PhD, the Mancias Lab studies critical aspects of the biology of pancreatic cancer to develop novel therapeutic approaches. The lab takes a comprehensive approach to advance our understanding of pancreatic cancer; combining biochemical, quantitative mass spectrometry-based proteomic, gene editing, cell biological, and mouse modeling techniques.
Dr. Mancias discovered that pancreatic cancers that have an altered KRAS gene are fueled by a metabolic pathway called “NCOA4-mediated ferritinophagy” that supplies iron for pancreatic cancer growth. Interestingly, NCOA4-mediated ferritinophagy is also a major mechanism of resistance to some of the newest drugs that target the gene KRAS. With support from the DEKM Fund, Dr. Mancias is working to identify and/or develop drugs that target the NCOA4-mediated ferritinophagy pathway. Importantly, given that NCOA4 is involved with causing resistance to some of the new drugs that target the gene KRAS, there is a particular focus on testing new drugs that target the NCOA4 pathway in combination with those that target the gene KRAS. Dr. Mancias is excited about this promising work, as it represents a potential therapeutic option for many patients diagnosed with pancreatic cancer. Philanthropy is essential for completing the experiments that show proof-of principle and advance these potential new therapies into clinical trials for patients.
“We are extremely grateful to the DEKM Fund for their generous contributions to lab for cancer biology,” says Dr. Mancias. “Without their support, we wouldn’t be able to make groundbreaking advances in developing new targets for pancreatic cancer therapies.”
