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KRAS突变在非小细胞肺癌获得性治疗耐药中的意义。

Implications of KRAS mutations in acquired resistance to treatment in NSCLC.

作者信息

Del Re Marzia, Rofi Eleonora, Restante Giuliana, Crucitta Stefania, Arrigoni Elena, Fogli Stefano, Di Maio Massimo, Petrini Iacopo, Danesi Romano

机构信息

Clinical Pharmacology and Pharmacogenetics Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Department of Oncology, University of Turin, Ordine Mauriziano Hospital, Turin, Italy.

出版信息

Oncotarget. 2017 Dec 21;9(5):6630-6643. doi: 10.18632/oncotarget.23553. eCollection 2018 Jan 19.

Abstract

RATIONALE

KRAS is the most common and, simultaneously, the most ambiguous oncogene implicated in human cancer. Despite KRAS mutations were identified in Non Small Cell Lung Cancers (NSCLCs) more than 20 years ago, selective and specific inhibitors aimed at directly abrogating KRAS activity are not yet available. Nevertheless, many therapeutic approaches have been developed potentially useful to treat NSCLC patients mutated for KRAS and refractory to both standard chemotherapy and targeted therapies.The focus of this review will be to provide an overview of the network related to the intricate molecular KRAS pathways, stressing on preclinical and clinical studies that investigate the predictive value of KRAS mutations in NSCLC patients.

MATERIALS AND METHODS

A bibliographic search of the Medline database was conducted for articles published in English, with the keywords KRAS, KRAS mutations in non-small cell lung cancer, KRAS and tumorigenesis, KRAS and TKIs, KRAS and chemotherapy, KRAS and monoclonal antibody, KRAS and immunotherapy, KRAS and drugs, KRAS and drug resistance.

摘要

原理

KRAS是人类癌症中最常见且同时也是最具争议的致癌基因。尽管20多年前就在非小细胞肺癌(NSCLC)中发现了KRAS突变,但目前仍没有旨在直接消除KRAS活性的选择性和特异性抑制剂。然而,已经开发出许多治疗方法,可能对治疗KRAS突变且对标准化疗和靶向治疗均耐药的NSCLC患者有用。本综述的重点是概述与复杂的分子KRAS途径相关的网络,着重介绍研究NSCLC患者中KRAS突变预测价值的临床前和临床研究。

材料和方法

对Medline数据库进行文献检索,以查找用英文发表的文章,关键词为KRAS、非小细胞肺癌中的KRAS突变、KRAS与肿瘤发生、KRAS与酪氨酸激酶抑制剂、KRAS与化疗、KRAS与单克隆抗体、KRAS与免疫疗法、KRAS与药物、KRAS与耐药性。

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