Targeting ALK in patients with advanced Non Small Cell Lung Cancer: Biology, diagnostic and therapeutic options

Chiara Lazzari, Gianluca Spitaleri, Chiara Catania, Massimo Barberis, Cristina Noberasco, Mariacarmela Santarpia, Angelo Delmonte, Francesca Toffalorio, Fabio Conforti, Tommaso Martino De Pas

Research output: Contribution to journalArticle

Abstract

The discovery of EML4-ALK fusion gene in a subgroup of patients with lung adenocarcinoma led to the development of a new class of agents, the ALK inhibitors, and dramatically improved the clinical outcome of these patients. The striking results from clinical trials with crizotinib, the first ALK inhibitor evaluated, allowed the accelerated approval of crizotinib from the USA Food and Drug Administration (FDA). Despite the high initial results, patients acquire resistance to crizotinib, and different next generation ALK kinase inhibitors have been developed. In the current review, we will analyze the biology of EML4-ALK gene, the acquired resistance mechanisms to crizotinib, the therapeutic strategies, currently under evaluation, designed to overcome crizotinib resistance, and the open issues that need to be addressed in order to improve outcome in ALK+ Non Small Cell Lung Cancer (NSCLC) patients.

Original languageEnglish
Pages (from-to)358-365
Number of pages8
JournalCritical Reviews in Oncology/Hematology
Volume89
Issue number3
DOIs
Publication statusPublished - Mar 2014

Keywords

  • Crizotinib
  • EML4-ALK fusion gene
  • Non Small Cell Lung Cancer

ASJC Scopus subject areas

  • Oncology
  • Hematology
  • Geriatrics and Gerontology

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