Overcoming drug resistance to receptor tyrosine kinase inhibitors: Learning from lung cancer

被引：55

作者：

Kuwano, Michihiko ^{[1
,2
]}

Sonoda, Kahori ^{[2
]}

Murakami, Yuichi ^{[1
,2
]}

Watari, Kosuke ^{[2
]}

Ono, Mayumi ^{[2
]}

机构：

[1] St Marys Hosp, St Marys Inst Hlth Sci, Canc Translat Res Ctr, Kurume, Fukuoka 8308543, Japan

[2] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Pharmaceut Oncol, Fukuoka 8128582, Japan

来源：

PHARMACOLOGY & THERAPEUTICS | 2016年 / 161卷

关键词：

Targeted receptor TKIs; Acquired resistance to receptor TKIs; Overcoming drug resistance; Driver oncogenes; Gate keeper receptor mutations; Bypass signaling molecules; GROWTH-FACTOR RECEPTOR; BIM DELETION POLYMORPHISM; EGFR-TKI RESISTANCE; GENE COPY NUMBER; ACQUIRED-RESISTANCE; T790M MUTATIONS; MET AMPLIFICATION; TARGETED THERAPY; GEFITINIB RESISTANCE; ACTIVATING MUTATIONS;

D O I：

10.1016/j.pharmthera.2016.03.002

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

There are various receptor tyrosine kinase (TIC)-targeted drugs that are currently used in the treatment of patients with non-small cell lung cancer (NSCLC). Among them, the epidermal growth factor receptor (EGFR) TIC inhibitors (TKIs) are the most extensively studied. Receptor TKIs including EGFR TKIs have shown dramatic therapeutic efficacies in malignant tumors, which harbor activating mutations in the EGFR gene. However, within 1 or 2 years after treatment, patients harboring these mutations often develop resistance to TKI therapy. This review article is aimed at drawing attention to the fact that we must first understand how receptor TKI resistance is acquired to develop strategies for overcoming resistance to TKIs. Furthermore, an insight into the specific molecules or signaling pathways that mediate resistance is a key factor for understanding and overcoming acquired drug resistance. Finally, we present our views on the continuing battle against "drug resistance," and provide further guidelines and strategies on how to minimize the development of drug-resistant tumors. (C) 2016 Elsevier Inc. All rights reserved.

引用

页码：97 / 110

页数：14

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