Novel targeted therapies for resistant ALK-rearranged non-small-cell lung cancer: Ceritinib and beyond

Zeyad Kanaan, Goetz H. Kloecker, Ajit Paintal, Cesar A. Perez*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)885-892
Number of pages8
JournalOncoTargets and Therapy
Volume8
DOIs
StatePublished - Apr 20 2015

Keywords

  • ALK inhibitor
  • Crizotinib
  • EML4-ALK rearrangement
  • Vysis

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

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