Targeting the Serine/Threonine Protein Phosphatase-5 in Kidney Cancer
Abstract
About 74,000 people develop kidney cancer and approximately 15,000 patients die from this disease in the United States each year. Tobacco smoking, obesity, and exposure to organic solvents, heavy metals, herbicides, and petrochemicals all play a major role in development of kidney cancer. Members of the military are exposed to hazardous environments due to the nature of their service and deployments and thus are at risk of developing kidney cancer. These risk factors have been published and they include the following: (1) Cheap tobacco prices have been identified by enlisted personnel and Department of Defense health policy experts as promoting a culture of tobacco use in the U.S. military. Smoking doubles the risk of RCC in members of the military; (2) Higher incidence of kidney cancer in men versus women (2:1 ratio); (3) Incidence of kidney cancer in Veterans of Operation Ranch Hand, the unit responsible for aerially spraying herbicides in Vietnam; (4) Obesity among the non-active duty; (5) Military families are at risk because of environmental exposures. Traditional radiation and chemotherapies are ineffective in patients with kidney cancer and ~50% of patients develop metastatic disease; in these patients the 5-year survival rate is only ~10%. Such grim statistics point to an urgent need for better understanding of the kidney cancer biology and also for developing better therapeutic strategies. This project will decipher the mechanisms involved in regulation of a serine/threonine protein phosphatase-5 (PP5), which plays a prosurvival role in renal cancer. This project will also evaluate the drugs that target the regulators of PP5 therefore providing novel therapeutic strategies in treating renal cancer. This proposal is related to the FY19 KCRP therapeutic development area of emphasis. Based on our published work, we believe that PP5 silences the cell death pathway in the most common type of kidney cancer, clear cell renal cell carcinoma. We have rationally designed drugs that specifically bind and inhibit the PP5 phosphatase protein therefore activating the cells death pathway in ccRCC. This consequently leads to destruction of the kidney cancer. We believe that our efforts will benefit the Military, Veterans, other military beneficiaries, and the American public by reducing both pain and loss of life. Finally, our approach is expected to open a new therapeutic horizon that differs from the current treatment of patients with advanced kidney cancer. This is innovative, in our opinion, because it represents a major departure from the status quo by shifting the focus onto a target that kidney cancer cells depend on for their survival.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010831
Entities
People
- Mehdi Mollapour
Organizations
- State University of New York Upstate Medical University
- United States Army