Project 4 - Lung

Lung cancer is a prominent source of cancer health disparity. Despite Black and/or African American (B/AA) men and women having lower exposure to cigarette smoke, the main cause of lung cancer, B/AA men have a higher risk for lung cancer than White men and the 5-year survival of B/AA men and women is below that of White subjects. Biological factors may explain these disparities and may have wide-ranging effects including metabolism of inhaled carcinogens or anti-cancer therapeutics, and racial differences can impact the propensity to develop driver gene mutations. Unfortunately, there is a notable lack of cell line models for lung adenocarcinoma (LUAD) from B/AA patients, with no cell lines from alveolar epithelial cells (the LUAD progenitors) from B/AA individuals and only 5 known LUAD cell lines from B/AA individuals (vs. 71 LUAD cell lines from White subjects). Moreover, while targeted therapies are available for a subset of LUAD, in vitro systems to test therapeutics among B/AA individuals are sorely lacking. Therefore, to understand the biological underpinnings of the large disparity of lung cancer development and treatment between B/AA and White individuals, we need to i) characterize the driver mutations in lung adenocarcinoma (the most common type of lung cancer) among B/AA, and ii) develop in vitro lung cancer model systems that reflect the relevant mutations in the correct genetic background. We hypothesize that LUAD in B/AA individuals will have a unique repertoire of cancer driver genes due to genetic differences and will respond to targeted therapies distinctly from LUAD of White subjects. Our preliminary pilot work during Cycle 1 of funding led to the development of 3D-printed alveolar models and showed that polyisoprenylated-cysteinyl amide inhibitors (PCAIs) have the potential to be effective therapies for B/AA lung cancer. This project aims to follow-up on these findings and fill critical gaps in the knowledge and tools required to effectively treat lung adenocarcinoma in B/AA individuals.