title: Novel targeted therapies for resistant ALK-rearranged non-small-cell lung cancer: ceritinib and beyond.
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.
authors.affiliation: Division of Medical Oncology and Hematology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
authors.forename: Zeyad
authors.initials: Z
authors.lastname: Kanaan
authors.affiliation: Division of Medical Oncology and Hematology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
authors.forename: Goetz H
authors.initials: GH
authors.lastname: Kloecker
authors.affiliation: Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Ajit
authors.initials: A
authors.lastname: Paintal
authors.affiliation: Division of Medical Oncology and Hematology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Perez
keywords: ALK inhibitor; EML4-ALK rearrangement; Vysis; crizotinib