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Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
07:59

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ALK inhibition for non-small cell lung cancer: from discovery to therapy in record time

David E Gerber1, John D Minna

  • 1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, 75390, USA. david.gerber@utsouthwestern.edu

Cancer Cell
|December 16, 2010
PubMed

Insights

A new ALK inhibitor, crizotinib, offers significant clinical benefits for advanced non-small cell lung cancer (NSCLC) patients with EML4-ALK fusions. Researchers also identified mechanisms of resistance to this targeted therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • A specific genetic alteration, the EML4-ALK fusion oncogene, drives a subset of non-small cell lung cancer (NSCLC).
  • Tumor cells harboring this fusion are critically dependent on the EML4-ALK oncoprotein for their growth and survival.

Purpose of the Study:

  • To evaluate the efficacy and safety of crizotinib, an oral ALK inhibitor, in patients with advanced NSCLC harboring the EML4-ALK fusion.
  • To identify mechanisms of acquired resistance to crizotinib therapy.

Main Methods:

  • Clinical trial evaluating crizotinib in advanced NSCLC patients with EML4-ALK fusion.
  • Identification and characterization of resistance mechanisms.

Main Results:

  • Crizotinib demonstrated substantial clinical benefit with a favorable toxicity profile in patients with advanced NSCLC and EML4-ALK fusions.
  • A mechanism of clinical resistance to crizotinib was identified, highlighting the adaptive nature of cancer cells.

Conclusions:

  • Targeted therapy against oncogenic proteins, such as crizotinib for EML4-ALK positive NSCLC, represents a paradigm shift towards personalized medicine.
  • Genome-wide analysis of tumors is crucial for discovering novel therapeutic targets and overcoming treatment resistance.

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