학술논문

Novel targeted therapies for resistant ALK-rearranged non-small-cell lung cancer: ceritinib and beyond
Document Type
article
Source
OncoTargets and Therapy, Vol 2015, Iss default, Pp 885-892 (2015)
Subject
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Language
English
ISSN
1178-6930
Abstract
Zeyad Kanaan,1 Goetz H Kloecker,1 Ajit Paintal,2 Cesar A Perez1 1Division of Medical Oncology and Hematology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 2Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA Abstract: Lung cancer is the leading cause of cancer-related mortality in both sexes, accounting for over one quarter of cancer deaths. Non-small-cell lung cancer (NSCLC) comprises 85%–90% of lung cancer diagnoses and despite advances in multimodality therapies, 5-year survival rates remain dismal with a median survival for patients with metastatic disease of 1 year. The positive outcomes of targeted therapies against the kinase domain of epidermal growth factor receptor in NSCLC triggered consistent efforts to identify the so-called driver mutations as other potential targets. Anaplastic large-cell kinase (ALK) gene rearrangements were identified and targeted resulting in promising response rates in early studies. Unfortunately, most of the patients treated with crizotinib, the first-generation ALK inhibitor, progressed within 9 months. Ceritinib is a second-generation ALK inhibitor that has demonstrated activity in crizotinib-resistant patients, becoming a promising treatment option in this population. Furthermore, additional novel ALK inhibitors and agents targeting alternative pathways have been recruited to rechallenge this evasive disease post-crizotinib resistance. Keywords: crizotinib, EML4-ALK rearrangement, Vysis, ALK inhibitor