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World J Clin Oncol. Oct 10, 2014; 5(4): 576-587
Published online Oct 10, 2014. doi: 10.5306/wjco.v5.i4.576
Review of the current targeted therapies for non-small-cell lung cancer
Kim-Son H Nguyen, Joel W Neal, Heather Wakelee
Kim-Son H Nguyen, Joel W Neal, Heather Wakelee, Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, United States
Author contributions: All authors contributed equally to this paper.
Correspondence to: Heather Wakelee, MD, Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, United States. hwakelee@stanford.edu
Telephone: +1-650-7367221 Fax: +1-650-7243697
Received: February 10, 2014
Revised: May 7, 2014
Accepted: May 28, 2014
Published online: October 10, 2014
Processing time: 172 Days and 12.9 Hours
Abstract

The last decade has witnessed the development of oncogene-directed targeted therapies that have significantly changed the treatment of non-small-cell lung cancer (NSCLC). In this paper we review the data demonstrating efficacy of gefitinib, erlotinib, and afatinib, which target the epidermal growth factor receptor (EGFR), and crizotinib which targets anaplastic lymphoma kinase (ALK). We discuss the challenge of acquired resistance to these small-molecular tyrosine kinase inhibitors and review promising agents which may overcome resistance, including the EGFR T790M-targeted agents CO-1686 and AZD9291, and the ALK-targeted agents ceritinib (LDK378), AP26113, alectinib (CH/RO5424802), and others. Emerging therapies directed against other driver oncogenes in NSCLC including ROS1, HER2, and BRAF are covered as well. The identification of specific molecular targets in a significant fraction of NSCLC has led to the personalized deployment of many effective targeted therapies, with more to come.

Keywords: Lung cancer; Non-small cell lung cancer; Targeted therapies; Epidermal growth factor receptor; Epidermal growth factor receptor; Anaplastic lymphoma kinase; Anaplastic lymphoma kinase; Acquired resistance

Core tip: The development of oncogene-directed targeted therapies has significantly changed the treatment of non-small-cell lung cancer. We review the data demonstrating efficacy of small-molecule tyrosine kinase inhibitors against epidermal growth factor receptor, anaplastic lymphoma kinase, ROS1, and other oncogenes. We also discuss the challenge of acquired resistance to these therapies and review promising agents which may overcome resistance.