Anaplastic lymphoma kinase as a new target for the treatment of non-small-cell lung cancer.

Marcello Tiseo, Francesco Gelsomino, Marco Bartolotti, Paola Bordi, Melissa Bersanelli, Giulio Rossi, Andrea Ardizzoni

Research output: Contribution to journalArticlepeer-review


The anaplastic lymphoma kinase (ALK) gene rearrangement identifies a distinct molecular subset in non-small-cell lung cancer (NSCLC) populations susceptible to targeted inhibition. It consists of a small inversion in the short arm of chromosome 2 between exon 20 of the ALK gene and different exons of the echinoderm microtubule-associated protein-like (EML4) gene. This translocation leads to a chimeric protein with constitutive activation of ALK that possesses an oncogenic activity demonstrated both in vitro and in vivo. Other rare translocation partners for ALK other than EML4 may be found in lung cancers, including TRK-fused gene (TFG) and kinesin family member 5B (KIF5B). ALK-positive patients represent 5-6% of all NSCLCs and they seem to have particular clinicopathological and molecular features. Recently, Phase I-II trial results of crizotinib, a potent dual c-MET and ALK inhibitor, demonstrated its dramatic efficacy in ALK-positive patients with advanced NSCLC. This article will present knowledge on the characteristics of ALK-positive patients, discuss the different methods of ALK rearrangement detection and focus on clinical results of crizotinib.

Original languageEnglish
Pages (from-to)1677-1687
Number of pages11
JournalExpert Review of Anticancer Therapy
Issue number11
Publication statusPublished - Nov 2011

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Oncology

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