A New Therapeutic Target to Prevent Pancreatic Cancer Metastasis
Abstract
Scientific Objective and Rationale: Pancreatic ductal adenocarcinoma is the most common type of pancreatic cancer and the third leading cause of cancer death in the United States, with a 5-year survival rate of only about 10%. Even for patients for whom the cancer has not spread to other parts of the body (metastasis), tumor removal followed by chemotherapy and radiation therapy typically does not result in a clean bill of health. Indeed, 3-year survival rates following tumor removal have improved only modestly in recent years. Moreover, clinical studies that have tried various combinations of chemotherapy in patients with metastasis have improved their survival by only a few months. Furthermore, immunotherapy with checkpoint inhibitors, which has been quite effective in treating several other tumor types, has not yet shown benefit to patients suffering pancreatic cancer. Clearly, a new type of treatment for pancreatic ductal adenocarcinoma is needed to improve the well-being of those affected by it. Against this backdrop, the proposed project will investigate a new immunotherapy that is involved in not only controlling the antitumor immune response in the body, but also maintaining the self-renewal of cancer stem cells that seed tumor regrowth at either the original or new tumor sites in the body, which is responsible for recurrence and metastasis of the cancer -- especially in the case of pancreatic cancer. We will carry out our investigation using patient-derived organoids (a miniaturized and simplified version of an organ produced to study disease and treatment) and a mouse model of the disease, which will generate information necessary to bring this new immunotherapy to the clinic to help improve the outcomes of patients facing pancreatic cancer metastasis. The proposed project addresses this FY22 PCARP Focus Area: Understanding the events that promote pancreatic cancer metastasis Potential Impact of the Proposed Project on Pancreatic Cancer Research and/or Patient Care: We will carry out proposed project with cutting edge techniques. In particular, we will perform cross-species (human-mouse) transcriptomic analysis at the level of the single cell. This single-cell insight will help us determine the most effective and least toxic therapeutic combination to test in the mouse model. Determining this therapeutic combination will allow other researchers in the field of pancreatic cancer research to further develop this new immunotherapy and quickly deliver it to the clinic to better treat patients with pancreatic cancer. Potential Impact of the Proposed Project on Pancreatic Cancer Patients and Their Families and/or Caregivers: Currently, being diagnosed with pancreatic cancer essentially is a death sentence. In addition to the low survival rate, the standard treatments for pancreatic cancer still feature mostly chemotherapy drugs developed decades ago. Indeed, the toxicity of these drugs is so high that patients typically require caregivers or family members to help them with their daily routine. Moreover, these toxic therapies extend the lives of patients by only a few months. Knowing this, many pancreatic cancer patients choose not to receive chemotherapy. Meanwhile, immunotherapy has revolutionized the treatment of other cancers, resulting in long-term survival not previously seen with chemotherapy, likely due to the development of immunological memory against the tumors. To address these shortcomings, the proposed project will investigate a new immunotherapy for treating pancreatic cancer. In addition, because this new immunotherapy involves a first-in-class small molecule that was developed by Takeda Pharmaceuticals and exhibited excellent safety in Phase I trials, it will enable the results of the proposed project to easily and quickly be delivered to the clinic to improve the outcomes of pancreatic cancer patients. Overall, representing a team that spans the continuum from laboratory
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310559
Entities
People
- Yuan Chen
Organizations
- United States Army
- University of California, San Diego