Open AccessReview of the current targeted therapies for non-small-cell lung cancer
Author(s) -
Kim-Son H. Nguyen,
Joel W. Neal,
Heather A. Wakelee
Publication year - 2014
Publication title -
world journal of clinical oncology
Language(s) - English
Resource type - Journals
ISSN - 2218-4333
DOI - 10.5306/wjco.v5.i4.576
Subject(s) - crizotinib , medicine , afatinib , ceritinib , anaplastic lymphoma kinase , erlotinib , t790m , alectinib , targeted therapy , gefitinib , kras , epidermal growth factor receptor , ros1 , lung cancer , cancer research , tyrosine kinase , lapatinib , resistance mutation , cancer , oncology , trastuzumab , breast cancer , adenocarcinoma , receptor , biology , reverse transcriptase , malignant pleural effusion , gene , colorectal cancer , rna , biochemistry
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.