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Nguyen, Phong B. H.; Ohnmacht, Alexander J.; Sharifli, Samir; Garnett, Mathew J. and Menden, Michael P. (2021): Inferred Ancestral Origin of Cancer Cell Lines Associates with Differential Drug Response. In: International Journal of Molecular Sciences, Vol. 22, No. 18, 10135

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Disparities between risk, treatment outcomes and survival rates in cancer patients across the world may be attributed to socioeconomic factors. In addition, the role of ancestry is frequently discussed. In preclinical studies, high-throughput drug screens in cancer cell lines have empowered the identification of clinically relevant molecular biomarkers of drug sensitivity;however, the genetic ancestry from tissue donors has been largely neglected in this setting. In order to address this, here, we show that the inferred ancestry of cancer cell lines is conserved and may impact drug response in patients as a predictive covariate in high-throughput drug screens. We found that there are differential drug responses between European and East Asian ancestries, especially when treated with PI3K/mTOR inhibitors. Our finding emphasizes a new angle in precision medicine, as cancer intervention strategies should consider the germline landscape, thereby reducing the failure rate of clinical trials.

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