Current therapy of KRAS-mutant lung cancer.
Current therapy of KRAS-mutant lung cancer.
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KRAS突变肺癌的当前疗法。
DOI：
10.1007/s10555-020-09903-9
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Megyesfalvi Z
中科院分区：
文献类型：
--
作者：
Ghimessy A;Radeczky P;Laszlo V;Hegedus B;Renyi-Vamos F;Fillinger J;Klepetko W;Lang C;Dome B;Megyesfalvi Z
KRAS突变是西方国家肺腺癌（LADC）患者中最常见的功能获得性改变。尽管它们在几十年前就已经被鉴定出来，但之前用单药治疗方法靶向KRAS信号传导的努力，如法尼基转移酶抑制剂、异戊二烯化抑制、KRAS下游信号传导的损伤和合成致死性筛选，都没有成功。此外，KRAS癌基因在LADC中的作用仍未完全了解，其对标准治疗的预后和预测影响仍存在争议。值得注意的是，包括一般非小细胞肺癌（NSCLC）人群而不是LADC患者的KRAS相关研究应进行非常仔细的评估。然而，最近，全面的基因组分析和其他共同发生的遗传变异的广谱分析已经确定了独特的治疗弱点。新型靶向药物如共价KRAS G12C抑制剂或最近提出的组合方法是一些例子，它们可以为携带KRAS突变的LADC患者提供定制治疗。这篇综述总结了有关KRAS突变LADC治疗方法的当前知识，并提供了KRAS靶向抗癌策略的最新进展的最新信息，重点关注潜在的临床意义。
KRAS mutations are the most frequent gain-of-function alterations in patients with lung adenocarcinoma (LADC) in the Western world. Although they have been identified decades ago, prior efforts to target KRAS signaling with single-agent therapeutic approaches such as farnesyl transferase inhibitors, prenylation inhibition, impairment of KRAS downstream signaling, and synthetic lethality screens have been unsuccessful. Moreover, the role of KRAS oncogene in LADC is still not fully understood, and its prognostic and predictive impact with regards to the standard of care therapy remains controversial. Of note, KRAS-related studies that included general non-small cell lung cancer (NSCLC) population instead of LADC patients should be very carefully evaluated. Recently, however, comprehensive genomic profiling and wide-spectrum analysis of other co-occurring genetic alterations have identified unique therapeutic vulnerabilities. Novel targeted agents such as the covalent KRAS G12C inhibitors or the recently proposed combinatory approaches are some examples which may allow a tailored treatment for LADC patients harboring KRAS mutations. This review summarizes the current knowledge about the therapeutic approaches of KRAS-mutated LADC and provides an update on the most recent advances in KRAS-targeted anti-cancer strategies, with a focus on potential clinical implications.
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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
DOI：
10.1093/annonc/mdt205
发表时间：
2013-09
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Dearden S;Stevens J;Wu YL;Blowers D
通讯作者：
Blowers D
DOI：
10.1097/jto.0b013e31829923ec
发表时间：
2013-08
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Chaft JE;Rusch V;Ginsberg MS;Paik PK;Finley DJ;Kris MG;Price KA;Azzoli CG;Fury MG;Riely GJ;Krug LM;Downey RJ;Bains MS;Sima CS;Rizk N;Travis WD;Rizvi NA
通讯作者：
Rizvi NA
影响因子：
45.3
作者：
Eberhard, DA;Johnson, BE;Hillan, KJ
通讯作者：
Hillan, KJ
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