Effect of HSP70 in Immune Environment on Pancreatic Cancer Growth
Abstract
Pancreatic cancer is an aggressive disease with poor outcomes. Military population bears a significant brunt of this disease due to increased exposure to potential risk factors like tobacco and alcohol. Scientific community has not made much progress against pancreatic cancer. One of the reasons for insufficient progress is that the scientific research has primarily focused on killing tumor cells without due attention to the surrounding tissue, which supports tumor growth and metastases. The Principal Investigator (PI) on the current grant proposal, Dr. Vikas Dudeja, and his mentor, Dr. Ashok Saluja, have previously shown that heat shock protein 70 (HSP70), a survival protein that is overexpressed in cancer cells, promotes tumor growth and metastases. The Dudeja-Saluja team has now developed a novel drug that decreases HSP70 and kills cancer cells. This drug is currently in a Phase I clinical trial against advanced gastrointestinal malignancies. This drug will soon enter a Phase II clinical trial against pancreatic cancer. While the PI and his mentor have previously shown that HSP70 in cancer cells promotes tumor growth, the role of HSP70 in surrounding non-cancerous immune or stromal cells is not known. The preliminary data generated by the PI suggest that HSP70 in immune cells protects cancer cells from cell death and that if HSP70 is decreased in immune cells, the body?s own immunity kills cancer cells. These are significant observations as they suggest that by decreasing HSP70 in immune cells, one can harness immune cells? cancer fighting properties for therapeutic gain. In the current grant proposal, the PI, under guidance of his mentor, will first confirm these findings in multiple animal models. Then the PI will also find out the mechanism how HSP70 protects cancer cells from immune mediated killing. This is important as discovery of this mechanism will lead to development of strategies to decrease HSP70 in immune cells to treat patients with pancreatic cancer. Dr. Dudeja is committed to change the outcomes of patients with pancreatic cancer. He is a cancer surgeon by training and has spent the last 10 years studying pancreatic cancer in lab. He has an established mentor-mentee relationship with Dr. Ashok Saluja, who is a world-famous pancreatic cancer researcher. Dr. Saluja is currently Professor and Vice Chair in the Department of Surgery and Director of the Sylvester Pancreatic Cancer Research Institute at the University of Miami. He has successfully mentored 30 postdoctoral fellows and 20 clinicians scientists, who are now successful academicians throughout the world. His success in securing extramural funding, success in research, and strong commitment to his trainees makes him an ideal mentor. Dr. Dudeja has now joined the Department of Surgery at the University of Miami (U Miami) as a surgeon-scientist where he has 50% protected time from clinical duties and has access to significant resources devoted to pancreatic cancer basic science research. This position has been strategically chosen to provide proximity to his mentor and resources to support his basic science endeavor. The PI and his mentor together have great potential to change the outcomes of pancreatic cancer. This is evident from their track record. The Career Development Award will provide resources to continue the research described in the application. This will not only enhance his career and help establish him as a surgeon-scientist in the field of pancreatic cancer, but will also generate novel data that will help device novel therapies against pancreatic cancer. Successful execution of the proposed studies will help us understand the mechanism by which decreasing HSP70 in immune cells leads to immune mediated killing of cancer cells. This will guide the future research to develop therapies by which HSP70 in immune cells can be decreased, thus leading to development of effective therapies against pancreatic cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710392
Entities
People
- Vikas Dudeja
Organizations
- United States Army
- University of Miami