Abstract C093: Increasing racial diversity of lung adenocarcinoma cell lines to mitigate lung cancer health disparities

Abstract

Abstract Lung cancer is the leading cause of cancer death in the United States and worldwide, and a significant source of cancer health disparities. Black/African American (B/AA) men exhibit the highest rate of lung cancer death compared to any other racial group. Compared to White men, B/AA men have a 12% higher lung cancer incidence rate and a 15% higher lung cancer death rate. One essential tool in the study of lung cancer is the use of lung cancer cell lines, which can be applied to molecular studies of lung cancer development and progression and pre-clinical drug testing. To minimize disparities in lung cancer research, it is important that cell lines representing different lung cancer histological subtypes, carrying different cancer driver genes, and representing different races and ethnicities be available. This is particularly relevant for lung cancer cell lines from B/AA men. We reviewed the availability of lung cancer cell lines and observed a considerable imbalance in the representation of cell lines from different population groups. We identified over 800 lung cancer cell lines, with the majority of lung cancer cell lines derived from White and Asian patients, and only 31 lung cancer cell lines from B/AA patients. In addition, we did not find any cell lines from Hispanic/Latin(x) (H/L), American Indian/American Native (AI/AN), or Native Hawaiian or other Pacific Islander (NHOPI) patients. Focusing on lung adenocarcinoma, the most common type of lung cancer, we aim to increase the representation of B/AA cell lines by creating new cell lines from B/AA lung cancer patients, as well as by generating isogenic cell line variants from existing lung cancer cell lines, such as NCI-H23. NCI-H23 was derived from a Black male patient with a KRAS G12C heterozygous mutation. We use CRISPR/Cas9-based genome editing to replace the KRAS G12C mutation with other KRAS mutations found in B/AA patients, including KRAS G12V, KRAS G12A, and KRAS G13C. The lack of an appropriately diverse collection of lung cancer cell lines significantly limits racially and ethnically inclusive lung cancer research. This hinders the ability to develop inclusive models, screen comprehensively for therapeutic compounds, and pre-clinically test new drugs. Ultimately, this leads to an under-development of therapies that can increase the survival of minority and underserved patients. The noted lack of cell lines from underrepresented groups should mobilize researchers and clinicians to establish additional cell lines and ensure appropriate representation of all population groups in this critical pre-clinical research resource. Citation Format: Christopher Leon, Matthew Gladstone, Chunli Yan, Diana I. Romero, Yong Huang, Kweku Ofosu-Asante, Nazarius S. Lamango, Ite A. Offringa. Increasing racial diversity of lung adenocarcinoma cell lines to mitigate lung cancer health disparities [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C093.