Impact of Inhibition of KRAS/STK11-Induced Immune Suppression in Enhancing Immunotherapy Response
Abstract
Scientific objective and rationale: It is now well established that a functional immune system is crucial in controlling tumor growth. Importantly, recent studies have demonstrated the considerable potential of immunotherapy in treatment of lung as well as other cancer types. However, the response rates are still relatively low, suggesting that combination of immunotherapy with other treatments may be needed to enhance efficacy. It is important to note that benefit from immunotherapy is commonly associated with an active immune surveillance response in tumors. Cancer is initiated and driven by mutations in genes called oncogenes. The role and potential association between common lung cancer mutations and the immune surveillance response has however not been investigated. The studies proposed here will be among the first to define roles of major oncogene mutations in suppression of the immune surveillance response and will devise ways of overcoming this suppression to increase the response to immunotherapy. As such, we believe these studies can significantly impact one of the Lung Cancer Research Program Areas of Emphasis: "Identify innovative strategies for prevention and treatment of early and/or localized lung cancer." Applicability of the research: Key points related to the applicability of this research are summarized below. -- Types of patients: The research proposed here can provide substantial benefit to lung cancer patients. Moreover, since underlying mechanisms we are studying may also exist in other cancer types, the applicability of this research may be much broader. -- Clinical Applications: The most important goal of these studies is to determine whether drugs that suppress oncogene-induced effects can increase the response to immunotherapy. Importantly, the drugs we are testing were very recently approved by the Food and Drug Administration. Positive results from our studies can therefore be a very significant finding that is testable in human lung cancer patients in the near term. -- Clinical timeframe: We believe we can achieve a clinically useful outcome upon completion of this 2-year proposal. -- Impact on lung cancer research: The role and potential association between common lung cancer mutations and the immune surveillance response is not known. The studies proposed here will be among the first to define roles of major oncogene mutations in suppression of the immune surveillance response. In addition, we will develop approaches for overcoming this suppression to increase the response to immunotherapy. -- Project relevance: Lung cancer is the leading cause of cancer deaths worldwide. Despite some therapeutic advances over the last several decades, the overall 5-year survival remains very low. If successful, the studies proposed here may have a significant impact in reducing lung cancer mortality in military Service members as well as in the general population.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510376
Entities
People
- Amer Beg
Organizations
- H. Lee Moffitt Cancer Center & Research Institute
- United States Army