Targeting KRAS Mutant in Non-Small Cell Lung Cancer: Novel Insights Into Therapeutic Strategies.
Targeting KRAS Mutant in Non-Small Cell Lung Cancer: Novel Insights Into Therapeutic Strategies.
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靶向非小细胞肺癌中的KRAS突变：治疗策略的新见解。
DOI：
10.3389/fonc.2022.796832
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发表时间：
2022
影响因子：
4.7
通讯作者：
Ortiz-Cuaran S
中科院分区：
文献类型：
--
作者：
Désage AL;Léonce C;Swalduz A;Ortiz-Cuaran S
尽管KRAS激活突变是非小细胞肺癌（NSCLC）中最常见的致癌驱动因素，但在过去十年中，各种抑制KRAS的尝试都失败了。KRAS突变与不良预后和对标准治疗方案的不良反应有关。最近开发的新的治疗药物（即adagasib， sotorasib）特异性靶向KRAS G12C的gdp结合状态，证明了在治疗这一亚组患者方面取得了前所未有的成功。尽管提供了临床前和临床疗效，但对KRAS G12C抑制剂获得性耐药的几种机制已被报道。在这种情况下，包括抑制SHP2、SOS1或KRAS G12C下游效应物在内的联合治疗策略似乎对克服获得性耐药特别有意义。在这篇综述中，我们将讨论针对KRAS G12C的新治疗策略以及克服KRAS G12C抑制剂获得性耐药的有希望的联合治疗方法。
Although KRAS-activating mutations represent the most common oncogenic driver in non-small cell lung cancer (NSCLC), various attempts to inhibit KRAS failed in the past decade. KRAS mutations are associated with a poor prognosis and a poor response to standard therapeutic regimen. The recent development of new therapeutic agents (i.e., adagrasib, sotorasib) that target specifically KRAS G12C in its GDP-bound state has evidenced an unprecedented success in the treatment of this subgroup of patients. Despite providing pre-clinical and clinical efficacy, several mechanisms of acquired resistance to KRAS G12C inhibitors have been reported. In this setting, combined therapeutic strategies including inhibition of either SHP2, SOS1 or downstream effectors of KRAS G12C seem particularly interesting to overcome acquired resistance. In this review, we will discuss the novel therapeutic strategies targeting KRAS G12C and promising approaches of combined therapy to overcome acquired resistance to KRAS G12C inhibitors.
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同时发生的基因组改变对KRAS突变非小细胞肺癌患者结局的影响。
DOI：
10.1158/1078-0432.ccr-17-1841
发表时间：
2018-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Arbour KC;Jordan E;Kim HR;Dienstag J;Yu HA;Sanchez-Vega F;Lito P;Berger M;Solit DB;Hellmann M;Kris MG;Rudin CM;Ni A;Arcila M;Ladanyi M;Riely GJ
通讯作者：
Riely GJ
影响因子：
7.3
作者：
Fell, Jay B.;Fischer, John P.;Marx, Matthew A.
通讯作者：
Marx, Matthew A.
DOI：
10.1158/1078-0432.ccr-14-3214
发表时间：
2015-04-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cox AD;Der CJ;Philips MR
通讯作者：
Philips MR
影响因子：
11.5
作者：
Dong, Zhong-Yi;Zhong, Wen-Zhao;Wu, Yi-Long
通讯作者：
Wu, Yi-Long
影响因子：
8.8
作者：
Choughule, A.;Sharma, R.;Trivedi, V.;Thavamani, A.;Noronha, V.;Joshi, A.;Desai, S.;Chandrani, P.;Sundaram, P.;Utture, S.;Jambhekar, N.;Gupta, S.;Aich, J.;Prabhash, K.;Dutt, A.
通讯作者：
Dutt, A.