Sotorasib for the treatment of locally advanced/metastatic non-small cell lung cancer.

IF 3 4区 医学 Q2 ONCOLOGY Future oncology Pub Date : 2024-11-27 DOI:10.1080/14796694.2024.2430172
Jordyn P Higgins, Jennifer W Carlisle, Nader H Moniri, Shruti Gupta, Eziafa I Oduah, Ticiana Leal
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Abstract

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is prognostic of poor survival for patients with non-small cell lung cancer (NSCLC). KRAS G12C mutations occur in 13% of NSCLC cases and despite the frequency of this mutation, advances in drug development against KRAS have historically been impeded due to the extremely high affinity of KRAS for guanosine triphosphate (GTP) and the lack of a binding pocket on the surface of KRAS that is suitable for drug binding. Sotorasib, a first-in-class, highly selective KRAS G12C inhibitor overcomes this issue by irreversibly binding in the switch-II pocket. Sotorasib was granted accelerated FDA approval for the treatment of KRASG12C-mutated locally advanced/metastatic NSCLC who have received at least one prior systemic therapy. This review summarizes the pharmacology, clinical efficacy, adverse effects, and clinical considerations of sotorasib.

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索托拉西布用于治疗局部晚期/转移性非小细胞肺癌。
柯氏大鼠肉瘤病毒癌基因同源体(KRAS)突变是非小细胞肺癌(NSCLC)患者生存率低的预兆。尽管这种突变很常见,但由于 KRAS 对三磷酸鸟苷 (GTP) 的亲和力极高,而且 KRAS 表面缺乏适合药物结合的结合袋,因此针对 KRAS 的药物开发一直受阻。Sotorasib 是第一类高选择性 KRAS G12C 抑制剂,通过不可逆地与开关 II 口袋结合,克服了这一问题。索托拉西布已获得美国食品药品管理局(FDA)的加速批准,用于治疗既往至少接受过一次系统治疗的 KRASG12C 突变局部晚期/转移性 NSCLC。本综述概述了索拉西布的药理、临床疗效、不良反应和临床注意事项。
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来源期刊
Future oncology
Future oncology ONCOLOGY-
CiteScore
5.40
自引率
3.00%
发文量
335
审稿时长
4-8 weeks
期刊介绍: Future Oncology (ISSN 1479-6694) provides a forum for a new era of cancer care. The journal focuses on the most important advances and highlights their relevance in the clinical setting. Furthermore, Future Oncology delivers essential information in concise, at-a-glance article formats - vital in delivering information to an increasingly time-constrained community. The journal takes a forward-looking stance toward the scientific and clinical issues, together with the economic and policy issues that confront us in this new era of cancer care. The journal includes literature awareness such as the latest developments in radiotherapy and immunotherapy, concise commentary and analysis, and full review articles all of which provide key findings, translational to the clinical setting.
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