Developing immortalized human alveolar epithelial cell models to study lung adenocarcinoma in Black Americans

Abstract Lung cancer is a source of racial disparity among Black Americans, especially men. Despite lower tobacco exposure among Black men than White men, Black men are 37% more likely to develop lung cancer. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer in all ethnic/racial groups, including Blacks. KRASis the most frequently mutated driver gene in Black LUAD (~30%), and NRAS mutations are also seen (1-2%). A given oncogenic mutation could have different effects on a patient based on their racial/ethnic genetic background. Thus, studying the appropriate driver mutations in the correct model and genetic background is essential. Unfortunately, to our knowledge, there is only one LUAD cell line from a Black subject. Therefore, we are deriving immortalized human alveolar epithelial cell (hAEC) lines from Black Americans to develop models to study lung adenocarcinoma in Blacks. The Offringa lab has recently developed a rapid method to generate hAEC lines. We have generated three distinct hAEC lines from de-identified remnant transplant lungs from White Americans. Here, we will use the same method to establish new hAEC lines from de-identified human remnant transplant lungs from Black American subjects. hAECs grow well in 2-dimensional (2D) cultures as epithelial monolayers are capable of forming alveolar-like organoids in 3-dimensional (3D) cultures with fibroblasts and Matrigel. We will introduce the KRAS driver mutation alone or in combination with other oncogenes into the hAECs using CRISPR/Cas9 editing. The cell lines will be used to test KRAS-targeting therapeutics, including polyisoprenylated cysteinyl amide inhibitors (PCAIs). These agents have been shown to disrupt RAS-mediated signaling in ethnically/racially diverse cell lines. Our approach yields new cell lines that provide a valuable system to study LUAD in Black Americans. Through our research, we intend to address one facet of the prominent lack of representation of Black Americans in LUAD studies. Citation Format: Pablo E. Puente, Chunli Yan, Matthew Gregory, Nadine Belony, Nazarius Lamango, Yong Huang, Ite A. Offringa. Developing immortalized human alveolar epithelial cell models to study lung adenocarcinoma in Black Americans [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A087.