Clinical challenges in targeting anaplastic lymphoma kinase in advanced non-small cell lung cancer

Namrata Vijayvergia, Ranee Mehra

Research output: Contribution to journalReview articlepeer-review

Abstract

The revolution in individualized therapy for patients with advanced non-small cell lung cancer (NSCLC) has seen the emergence of a number of molecularly targeted therapies for distinct patient molecular subgroups. Activating anaplastic lymphoma kinase (ALK)-gene rearrangement has been detected in 3-7 % of NSCLC cases, and the ALK inhibitor crizotinib is now an approved treatment for patients with tumors harboring this event. However, resistance to ALK-targeted therapies is a ubiquitous problem in the management of advanced ALK-positive NSCLC and can be mediated by secondary kinase mutations or the activation of compensatory alternative oncogenic drivers. New, more potent ALK inhibitors such as ceritinib (LDK378), alectinib (CH5424802), and AP26113 are now emerging, together with an increased knowledge of the molecular basis of resistance. There is a need to evaluate the optimal clinical application of these new agents, either as sequential therapies or in combination with other targeted agents, to combat resistance and prolong survival in patients with ALK-positive NSCLC. The remarkable clinical activity of ALK inhibitors also emphasizes the importance of optimal diagnostic testing algorithms, to ensure that all eligible patients receive these breakthrough therapies.

Original languageEnglish (US)
Pages (from-to)437-446
Number of pages10
JournalCancer Chemotherapy and Pharmacology
Volume74
Issue number3
DOIs
StatePublished - Sep 2014

Keywords

  • ALK inhibitors
  • Anaplastic lymphoma kinase
  • Diagnostics
  • Non-small cell lung cancer
  • Resistance

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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