Faculty, Staff and Student Publications

Language

English

Publication Date

3-3-2025

Journal

Cancer Discovery

DOI

10.1158/2159-8290.CD-24-0827

PMID

39601595

PMCID

PMC11875934

PubMedCentral® Posted Date

9-3-2025

PubMedCentral® Full Text Version

Author MSS

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.

Keywords

Humans, Neoplasms, Genomics, Antineoplastic Agents, Treatment Outcome

Published Open-Access

yes

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