Abstract 1004: Establishing lung adenocarcinoma cell lines to mitigate lung cancer health disparities

Abstract Lung cancer remains the leading cause of cancer death worldwide and is a pronounced source of cancer health disparities. Black/African American (B/AA) individuals demonstrate the highest lung cancer death rates when compared to other ethnic/racial groups. B/AA males exhibit a 15% higher lung cancer death rate and a 12% higher lung cancer incidence when compared to White males. Lung adenocarcinoma (LUAD) is the most common histological subtype in all races including B/AA. To study lung cancer and its related disparities, essential tools such as lung cancer cell lines are important; they can be used for molecular studies of lung cancer development, progression, development of new therapies and pre-clinical drug testing. We reviewed the literature (Leon et al. 2023, Frontiers in Oncology, Vol. 13, p. 1187585, 2023) and identified only 30 unique B/AA cell lines out of ~800 cell lines available, with the majority of cell lines being from White and Asian patients. Moreover, only 6 B/AA cell lines were derived from patients with LUAD. We are in the process of developing additional LUAD cell lines from patients as well as alveolar epithelial cell lines that can be used to model LUAD development. In addition, we are generating multiple independent isogenic cell line variants from existing lung cancer cell line NCI-H23, derived from a B/AA male patient harboring a KRASG12C heterozygous mutation. We are using CRISPR/Cas-9-based genome editing to replace the KRASG12C mutation with other KRAS mutations found in B/AA patients, including KRASG12V, KRASG12D, KRASG12A, and KRASG13C. We will perform whole genome sequencing to exclude off target effects of the CRISPR engineering. We will use isogenic cell lines to test the efficacy of polyisoprenylated cysteinyl amide inhibitors (PCAIs) and other drugs on cell lines bearing the different KRAS mutations. PCAIs were developed to target cells carrying mutant KRAS. Our efforts will provide tools to limit cancer health disparities and serve as a foundation for future research. Supported by grants U54CA233396, U54CA233444, and U54CA233465 from the National Institutes of Health (NIH)/National Cancer Institute (NCI) and the Norris Comprehensive Cancer Center core grant, award number P30CA014089 from the NIH/NCI. Citation Format: Sofia Lugo, Christopher Leon, Matthew Gladstone, Chunli Yan, Nazarius S. Lamango, Ite A. Offringa, Kweku Ofosu-Asante, Yong Huang, Justin K. Mensah-Mamfo. Establishing lung adenocarcinoma cell lines to mitigate lung cancer health disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1004.