TY - JOUR
T1 - Overcoming drug resistance to receptor tyrosine kinase inhibitors
T2 - Learning from lung cancer
AU - Kuwano, Michihiko
AU - Sonoda, Kahori
AU - Murakami, Yuichi
AU - Watari, Kosuke
AU - Ono, Mayumi
N1 - Funding Information:
We thank Yoshio Ide (St. Mary's Hospital) and Seiji Yano (Kanazawa University) for fruitful discussion. We also thank Yuri Shibao (Kyushu University) for illustration of figures and preparing this manuscript. This work was funded in part by JSPS KAKENHI Grant numbers 23112515 , 23300350 (M.O), by Life Science Foundation of Japan (M.O), by St. Mary's Institute of Health Sciences (M.K., M.O., K.W.) and also by Fukuoka Foundation for Sound Health (K.W.).
Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2016/5
Y1 - 2016/5
N2 - 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 firunderstand 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.
AB - 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 firunderstand 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.
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U2 - 10.1016/j.pharmthera.2016.03.002
DO - 10.1016/j.pharmthera.2016.03.002
M3 - Review article
C2 - 27000770
AN - SCOPUS:84961891781
VL - 161
SP - 97
EP - 110
JO - Pharmacology and Therapeutics, Part A: Chemotherapy, Toxicology and
JF - Pharmacology and Therapeutics, Part A: Chemotherapy, Toxicology and
SN - 0163-7258
ER -
