新一代 PI3Kα 抑制剂
A New Wave of PI3Kα Inhibitors.
机构信息
Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York.
Division of Hematology and Oncology, Department of Medicine, Columbia University, New York, New York.
出版信息
Cancer Discov. 2023 Nov 1;13(11):2313-2315. doi: 10.1158/2159-8290.CD-23-0945.
Abstract
This is the first peer-reviewed report of an allosteric, mutant-selective PI3Kα inhibitor, STX-478, that reduces PIK3CA-mutant tumor growth in mice. However, in contrast to the FDA-approved PI3Kα isoform-selective inhibitor alpelisib, STX-478 does not induce hyperglycemia or other metabolic dysfunctions. See related article by Buckbinder et al., p. 2432 (7).
摘要
这是首例具有变构作用的、突变选择性的 PI3Kα 抑制剂 STX-478 减少小鼠中 PIK3CA 突变肿瘤生长的同行评审报告。然而，与 FDA 批准的 PI3Kα 同工型选择性抑制剂 alpelisib 不同，STX-478 不会引起高血糖或其他代谢功能障碍。见 Buckbinder 等人的相关文章，第 2432 页（7）。
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本文引用的文献
1
STX-478, a Mutant-Selective, Allosteric PI3Kα Inhibitor Spares Metabolic Dysfunction and Improves Therapeutic Response in PI3Kα-Mutant Xenografts.STX-478，一种突变选择性、变构的 PI3Kα 抑制剂，可避免代谢功能障碍，并改善 PI3Kα 突变异种移植物的治疗反应。
Cancer Discov. 2023 Nov 1;13(11):2432-2447. doi: 10.1158/2159-8290.CD-23-0396.
2
At a crossroads: how to translate the roles of PI3K in oncogenic and metabolic signalling into improvements in cancer therapy.处于十字路口：如何将 PI3K 在致癌和代谢信号中的作用转化为癌症治疗的改善。
Nat Rev Clin Oncol. 2022 Jul;19(7):471-485. doi: 10.1038/s41571-022-00633-1. Epub 2022 Apr 28.
3
Factors leading to alpelisib discontinuation in patients with hormone receptor positive, human epidermal growth factor receptor-2 negative breast cancer.导致激素受体阳性、人表皮生长因子受体-2 阴性乳腺癌患者停用 alpelisib 的因素。
Breast Cancer Res Treat. 2022 Apr;192(2):303-311. doi: 10.1007/s10549-021-06476-1. Epub 2022 Jan 9.
4
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Lancet Oncol. 2017 Jul;18(7):904-916. doi: 10.1016/S1470-2045(17)30376-5. Epub 2017 May 30.
9
mTORC1 inhibition is required for sensitivity to PI3K p110α inhibitors in PIK3CA-mutant breast cancer.mTORC1 抑制是 PIK3CA 突变型乳腺癌对 PI3K p110α 抑制剂敏感所必需的。
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