All Roads Lead to Rome: YAP/TAZ Activity Influences Efficacy of KRASG12C Inhibitors.
All Roads Lead to Rome: YAP/TAZ Activity Influences Efficacy of KRASG12C Inhibitors.
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条条大路通罗马：YAP/TAZ 活动影响 KRASG12C 抑制剂的功效。
DOI：
10.1158/0008-5472.can-23-3547
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发表时间：
2023
期刊：
影响因子：
11.2
通讯作者：
Haigis,KevinM
中科院分区：
文献类型：
--
作者：
Johnson,ChristianW;Haigis,KevinM
KRASG 12 C直接抑制剂的开发代表了肿瘤学领域的巨大进步。然而，有相当大的机会，以提高响应率KRASG 12 C抑制剂。在这一期的《癌症研究》中，三个研究小组使用基于CRISPR的敲除筛选探索了KRASG 12 C抑制剂在肺癌、结直肠癌和胰腺癌中的活性调节。虽然每个小组都鉴定并验证了赋予对KRASG 12 C抑制的抗性的多种基因和途径，但所有三个小组都将雅普/TAZ的活化作为抗性的常见手段。虽然KRASG 12 C和雅普/TAZ的共抑制在异种移植模型中不引起完全的肿瘤消退，但是组合雅普/TAZ抑制能够显著延长肿瘤对KRASG 12抑制的反应。第4095页，Edwards等人，第4112页，以及Prahallad等人，第4130页
The development of direct inhibitors of KRASG12Crepresents a monumental step forward in the field of oncology. Nevertheless, there is considerable opportunity to enhance response rates to KRASG12Cinhibitors. In this issue ofCancer Research, three investigative teams explore the modulation of KRASG12Cinhibitor activity in lung, colorectal, and pancreatic cancers using CRISPR-based knockout screens. While each group identified and validated a variety of genes and pathways conferring resistance to KRASG12Cinhibition, all three groups converged upon activation of YAP/TAZ as a common means of resistance. While coinhibition of KRASG12Cand YAP/TAZ did not cause complete tumor regression in xenograft models, combining YAP/TAZ inhibition was capable of significantly extending the response of tumors to KRASG12Cinhibition.See related articles by Mukhopadhyay et al., p. 4095, Edwards et al., p. 4112, and Prahallad et al., p. 4130