PROFILing non-small-cell lung cancer patients for treatment with crizotinib according to anaplastic lymphoma kinase abnormalities: translating science into medicine

Abstract

Introduction: In the recent years, the growing attention to the molecular background of non-small-cell lung cancer (NSCLC) led to the identification of different molecular subtypes according to genetic abnormalities driving the disease development and progression. Whereas the addicted pathways were successfully inhibited (such as the mutant epidermal growth factor receptor), clinicians have witnessed a dramatic survival improvement. In this regard, the molecular portrait of adenocarcinoma was recently enriched by the identification of a specific patients' subgroup characterized by abnormalities in the anaplastic lymphoma kinase (ALK), with unclear prognostic features but impressive response to specific inhibitors.

Areas covered: In this article, updated data derived from the development and the use of crizotinib (the most advanced in development among tyrosine kinase ALK inhibitors) in comparison with standard second-line chemotherapy for patients affected by ALK-altered NSCLC are reviewed.

Expert opinion: Taking into account the available data, pretreated NSCLC patients carrying the ALK-translocation require a selected targeted therapy which significantly improves activity, efficacy and symptoms control versus chemotherapy. In this context, the identification of this disease entity and the availability of such impressive therapeutic targeting represent a further step toward the understanding of the molecular complexity behind the adenocarcinoma of the lung.

Keywords::

• adenocarcinoma
• anaplastic lymphoma kinase
• crizotinib
• lung cancer
• tyrosine kinase

Declaration of interest

M Milella has received speaker's fee and advisory board participation from Eli-Lilly; speaker's fee from AstraZeneca. Giampaolo Tortora has done consultancy for Novartis, Pfizer, GSK. E Bria is on the advisory board for Eli-Lilly, Pfizer, Amgen and has received speaker's fee from Eli-Lilly. The remaining authors have no conflicts of interest. This work was supported in part by grants from the Italian Association for Cancer Research (AIRC 5 x mille Special Program on Clinical and Molecular Oncology and IG 12182 and 12214), and the Italian Ministry of University and Research (MIUR-PRIN 2009X23L78_005). No writing assistance was utilized in the production of this manuscript.

Notes

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