癌症仍然是全球死亡的主要原因，已批准的肿瘤药物仍然存在不同的患者反应，并伴随着限制有效性的不良反应 (AE)。在这里，我们使用转化人类多能癌症干细胞 (CSC) 与能够区分异常自我更新和分化的健康干细胞 (hSC) 的替代模型，在干性背景下检查了超过 100 种 FDA 批准的肿瘤药物。尽管这些药物中有一部分没有作用（非活性），但较大一部分会影响 CSC（活性），并且一个独特的子集优先影响 CSC，而不是 hSC（选择性）。每种药物 FDA 认可靶标的单细胞基因表达和蛋白质分析提供了 CSC 与 hSC 反应的分子相关性。独特的是，针对 CSC 的选择性药物显示出临床疗效（通过总体生存率衡量）并减少了 AE。我们的研究结果表明，虽然无意，但一半的抗癌药物对 CSC 具有活性，并且与改善临床结果相关。基于这些发现，我们建议将 CSC 靶向能力作为早期肿瘤治疗开发的一项特性。版权所有 © 2024。由 Elsevier B.V. 出版。

Cancer remains the leading cause of death worldwide with approved oncology drugs continuing to have heterogenous patient responses and accompanied adverse effects (AEs) that limits effectiveness. Here, we examined >100 FDA-approved oncology drugs in the context of stemness using a surrogate model of transformed human pluripotent cancer stem cells (CSCs) vs. healthy stem cells (hSCs) capable of distinguishing abnormal self-renewal and differentiation. Although a proportion of these drugs had no effects (inactive), a larger portion affected CSCs (active), and a unique subset preferentially affected CSCs over hSCs (selective). Single cell gene expression and protein profiling of each drug's FDA recognized target provided a molecular correlation of responses in CSCs vs. hSCs. Uniquely, drugs selective for CSCs demonstrated clinical efficacy, measured by overall survival, and reduced AEs. Our findings reveal that while unintentional, half of anticancer drugs are active against CSCs and associated with improved clinical outcomes. Based on these findings, we suggest ability to target CSC targeting should be included as a property of early onco-therapeutic development.Copyright © 2024. Published by Elsevier B.V.