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非小细胞肺癌中针对KRAS:“非G12c”患者的旧有失败与新选择

Targeting KRAS in NSCLC: Old Failures and New Options for "Non-G12c" Patients.

作者信息

Jacobs Francesca, Cani Massimiliano, Malapelle Umberto, Novello Silvia, Napoli Valerio Maria, Bironzo Paolo

机构信息

Department of Oncology, University of Turin, AOU San Luigi Gonzaga, 10043 Turin, Italy.

Department of Public Health, University of Naples Federico II, 80138 Naples, Italy.

出版信息

Cancers (Basel). 2021 Dec 16;13(24):6332. doi: 10.3390/cancers13246332.

Abstract

Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene mutations are among the most common driver alterations in non-small cell lung cancer (NSCLC). Despite their high frequency, valid treatment options are still lacking, mainly due to an intrinsic complexity of both the protein structure and the downstream pathway. The increasing knowledge about different mutation subtypes and co-mutations has paved the way to several promising therapeutic strategies. Despite the best results so far having been obtained in patients harbouring KRAS exon 2 p.G12C mutation, even the treatment landscape of non-p.G12C KRAS mutation positive patients is predicted to change soon. This review provides a comprehensive and critical overview of ongoing studies into NSCLC patients with KRAS mutations other than p.G12C and discusses future scenarios that will hopefully change the story of this disease.

摘要

Kirsten 大鼠肉瘤病毒癌基因同源物(KRAS)基因突变是非小细胞肺癌(NSCLC)中最常见的驱动改变之一。尽管其发生率很高,但仍然缺乏有效的治疗选择,这主要是由于蛋白质结构和下游通路的内在复杂性。对不同突变亚型和共突变的认识不断增加,为几种有前景的治疗策略铺平了道路。尽管到目前为止,在携带KRAS外显子2 p.G12C突变的患者中取得了最佳结果,但预计非p.G12C KRAS突变阳性患者的治疗格局也将很快改变。这篇综述全面且批判性地概述了针对非p.G12C KRAS突变的NSCLC患者正在进行的研究,并讨论了有望改变这种疾病状况的未来前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eef/8699276/5201a6eb2ba4/cancers-13-06332-g001.jpg

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