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.

中文翻译：

---

抗癌治疗效果的祖先差异及其潜在的基因组和分子改变


系统的多组学分析揭示了祖先依赖性的分子改变，但它们对抗癌治疗效果的影响在很大程度上尚不清楚。在这里，我们分析了 ClinicalTrials.gov 的临床试验，发现只有 8,779/102,721 （8.5%） 肿瘤学临床试验发布了按种族/民族划分的入组信息。非白人人群的代表性不足表明，确定不同种族群体之间抗肿瘤治疗疗效的差异仍然具有挑战性。通过对临床可操作基因、估算的药物反应和免疫特征的全面分析，我们确定了不同祖先群体之间对靶向、化疗和免疫疗法的治疗反应的潜在差异。对多个独立队列的进一步分析证实了我们的一些主要发现。这种潜在的祖先效应也在响应 CAR-T 疗法和 PROTAC 等新兴新疗法时被发现。这些发现在一个综合门户网站 Ancestral Differences of Efficacy in Cancers （ADEC;https://hanlaboratory.com/ADEC） 中公开提供，以促进他们的进一步研究。