Ancestral differences in anti-cancer treatment efficacy and their underlying genomic and molecular alterations

Abstract Systematic multi-omics analysis revealed ancestry-dependent molecular alterations, but their impact on the efficacy of anti-cancer treatment is yet largely unknown. Here, 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 anti-tumor 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 response to targeted, chemo and immunotherapies 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 CAR-T therapy and PROTACs. These findings are made publicly available in a comprehensive web portal, Ancestral Differences of Efficacy in Cancers (ADEC; https://hanlaboratory.com/ADEC), to facilitate their further investigation.