Stratification of patients with KRAS-mutated advanced non-small cell lung cancer: improving prognostics.

Expert review of respiratory medicine Pub Date : 2023-07-01 Epub Date: 2023-10-27 DOI:10.1080/17476348.2023.2265810
Yuda Zhang, Fanxu Zeng, Shixuan Peng, Yangqian Chen, Wenjuan Jiang, Zhan Wang, Li Deng, Zhe Huang, Haoyue Qin, Huan Yan, Xing Zhang, Lin Zhang, Nong Yang, Qian Gong, Liang Zeng, Yongchang Zhang
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Abstract

Introduction: KRAS is the most frequently mutated oncogene in cancer and encodes a key signaling protein in tumors. Due to its high affinity for GTP and the lack of a large binding pocket that allosteric inhibitors can occupy, KRAS has long been considered 'non-druggable.' Finding effective treatment measures for patients with KRAS mutations is our top priority.

Areas covered: In this article, we will provide an overview of the KRAS pathway and review the current state of therapeutic strategies for targeting oncogenic KRAS, as well as their potential to improve outcomes in patients with KRAS-mutant malignancies. We will also discuss the development of these strategies and gave an outlook on prospects.

Expert opinion: KRAS mutations have posed a significant challenge in the treatment of advanced non-small cell lung cancer (NSCLC) over the past few decades. However, the emergence of immunotherapy and KRAS inhibitors, such as Sotorasib (AMG 510) and Adagrasib (MRTX849), has marked a new era in cancer therapy. As more research and clinical trials continue, we anticipate the development of more effective treatment strategies and better options for lung cancer patients.

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KRAS-突变晚期非小细胞肺癌癌症患者的分层:改善预后。
简介:KRAS是癌症中最常见的突变癌基因,编码肿瘤中的关键信号蛋白。由于KRAS对GTP的高亲和力,并且缺乏变构抑制剂可以占据的大结合口袋,长期以来一直被认为是“不可药用的”为KRAS突变患者找到有效的治疗措施是我们的首要任务。涵盖领域:在这篇文章中,我们将概述KRAS途径,并回顾靶向致癌KRAS的治疗策略的现状,以及它们在改善KRAS突变恶性肿瘤患者预后方面的潜力。我们还将讨论这些战略的发展,并对前景进行展望。专家意见:KRAS突变在过去几十年中对晚期癌症(NSCLC)的治疗提出了重大挑战。然而,免疫疗法和KRAS抑制剂的出现,如Sotorasib(AMG510)和Adagrasib(MRTX849),标志着癌症治疗进入了一个新时代。随着更多的研究和临床试验的继续,我们预计将为癌症患者开发更有效的治疗策略和更好的选择。
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