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Data from Ancestral Differences in Anticancer Treatment Efficacy and Their Underlying Genomic and Molecular Alterations

Posted on 2025-03-03 - 08:20
Abstract

Systematic multiomic analysis has revealed ancestry-dependent molecular alterations, but their impact on the efficacy of anticancer treatment is yet largely unknown. In this study, we analyzed clinical trials from ClinicalTrials.gov and found that only 8,779/102,721 (8.5%) oncology clinical trials posted information on enrollment by race/ethnicity. The underrepresentation of non-White populations suggests that it remains challenging to determine differences in the efficacy of antitumor treatments among different racial groups. Through a comprehensive analysis of clinically actionable genes, imputed drug responses, and immune features, we identified potential differences in treatment responses to targeted therapy, chemotherapy, and immunotherapy between different ancestral populations. Further analysis of multiple independent cohorts confirmed some of our key findings. Such potential ancestral effects are also identified in response to emerging new treatments like chimeric antigen receptor T-cell therapy and proteolysis-targeting chimeras. These findings are made publicly available in a comprehensive web portal, Ancestral Differences of Efficacy in Cancers (https://hanlaboratory.com/ADEC), to facilitate their further investigation.

Significance:

Our study charts a global landscape of ancestry-associated differences in therapeutic efficacy, highlighting the importance of considering ancestry in anticancer therapies.

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FUNDING

National Institutes of Health (NIH)

Health and Environmental Sciences Institute (HESI)

Ralph W. and Grace M. Showalter Research Trust Fund (Showalter Foundation)

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AUTHORS (14)

  • Mei Luo
    Jingwen Yang
    Alejandro A. Schäffer
    Chengxuan Chen
    Yuan Liu
    Yamei Chen
    Chunru Lin
    Lixia Diao
    Yong Zang
    Yanyan Lou
    Huda Salman
    Gordon B. Mills
    Eytan Ruppin
    Leng Han
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