Summary:PIK3CA, which encodes the p110α catalytic subunit of PI3Kα, is one of the most frequently genetically activated kinases in solid tumors. In this issue of Cancer Discovery, Song and colleagues report that the related PI3Kα inhibitors taselisib and inavolisib trigger receptor tyrosine kinase (RTK)–dependent degradation of the mutant p110α protein in breast cancer cells that are positive for HER2 RTK, limiting feedback-mediated drug resistance and potentially widening the therapeutic index of PI3Kα inhibition.See related article by Song et al., p. 204.

中文翻译：

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通过选择性降解精确靶向癌症中的突变 PI3Kα

摘要：PIK3CA 编码 PI3Kα 的 p110α 催化亚基，是实体瘤中最常见的基因激活激酶之一。在本期《Cancer Discovery》中，Song 及其同事报告说，相关 PI3Kα 抑制剂 taselisib 和 inavolisib 会触发 HER2 RTK 呈阳性的乳腺癌细胞中受体酪氨酸激酶 (RTK) 依赖性突变 p110α 蛋白的降解，从而限制反馈介导的药物耐药性并可能扩大 PI3Kα 抑制的治疗指数。参见 Song 等人的相关文章，第 17 页。204.