克拉斯
医学
临床试验
肺癌
外显率
肿瘤科
人口
靶向治疗
癌症
后天抵抗
内科学
生物信息学
癌症研究
结直肠癌
表型
遗传学
环境卫生
生物
基因
作者
Garth W. Strohbehn,Kamya Sankar,Angel Qin,Gregory P. Kalemkerian
标识
DOI:10.1080/14656566.2022.2134777
摘要
Improving the clinical outcomes of patients with KRASG12C-mutated non-small cell lung cancer (NSCLC), the majority of whom are current or former smokers, has been a barrier to improving population-level outcomes in NSCLC. Novel and effective KRASG12C inhibitors are emerging, and sotorasib is the first member of that class to achieve commercial availability.In this review, we survey the epidemiology of KRASG12C-mutated NSCLC, as well as sotorasib's chemistry, pharmacology, and clinical trial data.While sotorasib's development has been unique and exciting, questions persist regarding its intracranial penetrance, optimal dose, and efficacy relative to standard-of-care therapy. Improvements in the clinical activity of KRAS inhibition will hinge on better understanding of resistance mechanisms, the development of broad-spectrum inhibitors with activity beyond G12C mutations, and combination therapy targeting multiple mediators of KRAS signaling and alternative pathways. From a regulatory perspective, sotorasib's development may, in time, prove to be an instructive example for early-phase clinical trialists and regulators focused on dose optimization.
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