Exploring APOBEC 3B as a Novel Target for Squamous Cell Lung Cancer
Abstract
Lung cancer is the leading cause of cancer death among both men and women. There will be an estimated 160,000 deaths from lung cancer in 2014, accounting for 28% of all cancer deaths. The majority (>75%) of these lung cancers are due to non-small lung cell carcinoma (NSCLC) and include two predominant subtypes, adenocarcinoma and squamous cell lung carcinoma (SCC). Major advances have been made in treating lung adenocarcinomas guided by understanding the genetic makeup of the tumor and using molecularly targeted therapies using Iressa and Tarceva that are effective on those tumors expressing mutant forms of Epidermal Growth Factor Receptor (EGFR) and have led to improvements in patient outcomes. Dramatic responses to Iressa or Tarceva are typically observed in patients who are non-smokers that express mutant forms of the EGFR and comprise about 10% NSCLC. Unfortunately, those remaining patients who have SCC are more often smokers who do not express mutant forms of EGFR or respond to Iressa/Tarceva. Importantly, a recent Institute of Medicine report indicated that active duty military personnel and Veterans have a higher incidence of smoking than the general population. Of concern is that the rate of tobacco use has started to increase since 1998, underscoring the link between smoking and squamous cell lung cancer. There is a critical need to understand the molecular mechanisms that lead to various subtypes of lung cancer, in particular those underlying mechanisms for clinically significant SCC, and to identify innovative strategies including targeted therapies for early treatment. This proposal will explore the possibility that another protein, APOBEC3B, having DNA cytosine deaminase enzymatic activity may be involved in tumorigenesis in SCC. The role of APOBEC3B will be examined to confirm that this protein does play a role in tumor development. This may identify APOBEC3B as a new molecular target for designing therapies to treat patients with SCC.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510290
Entities
People
- Karen Anderson
Organizations
- United States Army
- Yale University