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

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• 作者：Michihiko Kuwano^a ; ^b ; ^{kuwano@phar.kyushu-u.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Kahori Sonoda^b ; Yuichi Murakami^a ; ^b ; Kosuke Watari^b ; Mayumi Ono^b
• 关键词：Targeted receptor TKIs ; Acquired resistance to receptor TKIs ; Overcoming drug resistance ; Driver oncogenes ; Gate keeper receptor mutations ; Bypass signaling molecules
• 刊名：Pharmacology and Therapeutics
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：161
• 期：Complete
• 页码：97-110
• 全文大小：1789 K

文摘

There are various receptor tyrosine kinase (TK)-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) TK 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.