Abstract
Abstract Lung cancer remains the leading cause of cancer-related deaths world-wide. Statistical data reveals significant difference in both lung cancer incidence and death rate between African-American (AA) and Caucasian (CA) populations in the United States. Although these disparities can be partially attributed to socio-economical reasons, the biological mechanisms underlying them are poorly understood. In this study, we compared the chemoresistance of cell lines derived from tumor tissues obtained from AA patients (H23, H292) versus CA patients (A549, H460). The cell lines were treated with FDA-approved anti-cancer drugs as well as with cardenolide analogues previously reported by our group to have anti-cancer properties. Irrespectively of drug class, cellular senescence appeared to develop more abundantly in cells derived from AA patients. However, AA-derived cell lines manifested higher drug resistance in comparison to CA-derived ones, especially to cardenolide analogues. Recovery experiments in drug-free media revealed faster and more efficient re-growth after long-term (2 weeks) drug treatment in AA-derived cell lines. Taken together, the data provides a potential role for cellular senescence as mechanism of the differential chemoresistance observed between AA and CA lung cancer cell lines, revealing new potential targets for anti-cancer therapy. Citation Format: Nina Semenova, Camille C. Robertson, Juan S. Yakisich, Robyn R. Ayscue, Anand K. Iyer, Neelam Azad. Cellular senescence as a potential mechanism underlying differences in chemoresistance between lung cancer cell lines derived from African-American and Caucasian patients [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 2247.
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