Sotorasib: a treatment for non-small cell lung cancer with the KRAS G12C mutation

被引:11
|
作者
Zheng, Xinting [1 ,2 ]
Luo, Jiamin [2 ]
Liu, Wei [1 ]
Ashby, Charles R., Jr. [3 ]
Chen, Zhe-Sheng [3 ,4 ]
Lin, Lizhu [1 ]
机构
[1] Guangzhou Univ Chinese Med, Canc Ctr, Affiliated Hosp 1, Guangzhou, Peoples R China
[2] Guangzhou Univ Chinese Med, Clin Med Sch 1, Guangzhou, Peoples R China
[3] St Johns Univ, Dept Pharmaceut Sci, Coll Pharm & Hlth Sci, New York, NY 11439 USA
[4] St Johns Univ, Inst Biotechnol, New York, NY 11439 USA
关键词
Sotorasib; Non-small cell lung cancer  (NSCLC); KRAS G12C mutation inhibitors; Solid  tumor therapy; Targeted cancer therapy; KRAS(G12C) INHIBITOR; AMG; 510; RAS; ACTIVATION; RESISTANCE; REGULATORS; MECHANISM;
D O I
10.1358/dot.2022.58.4.3400573
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Sotorasib, a direct inhibitor of the enzyme Kirsten rat sarcoma viral oncogene (KRAS) with the G12C mutation, was approved by the U.S. Food and Drug Administration (FDA), as a second-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) containing the KRAS G12C mutation, on the basis of results of a phase II clinical trial (CodeBreaK100). In this article, we review the mechanism of action of KRAS G12C inhibitors and the latest clinical trials with sotorasib to provide a comprehensive understanding of its efficacy and toxicity. We also review the mechanisms that produce resistance to the KRAS G12C inhibitors and the preclinical research related to combination treatments for KRAS G12C-mutated tumors. Currently, clinical data suggests that sotorasib monotherapy has significant efficacy in NSCLC patients with the KRAS G12C mutation and tolerable toxicity, and it could represent a novel targeted therapy. Additional research will be required to delineate the mechanisms of resistance to sotorasib and determine the efficacy and safety of combination therapy for the treatment of NSCLC containing the KRAS G12C mutation.
引用
收藏
页码:175 / 185
页数:11
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