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ALK inhibitors in non-small cell lung cancer: the latest evidence and developments

Ivana Sullivan1, David Planchard2

  • 1Gustave Roussy - Medical Oncology, Villejuif, France.

Therapeutic Advances in Medical Oncology
|January 12, 2016
PubMed

Insights

New anaplastic lymphoma kinase (ALK) inhibitors offer improved treatment for advanced non-small cell lung cancer (NSCLC) patients resistant to crizotinib. These novel therapies show promising results and a favorable toxicity profile.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Crizotinib revolutionized advanced non-small cell lung cancer (NSCLC) treatment in patients with anaplastic lymphoma kinase (ALK) rearrangements.
  • Most patients develop resistance to crizotinib within a year due to acquired resistance mutations.
  • This necessitates the development of next-generation ALK inhibitors.

Purpose of the Study:

  • To review the molecular and clinical properties of newly developed ALK inhibitors.
  • To discuss their potential in treating crizotinib-resistant ALK-positive NSCLC.

Main Methods:

  • Review of current literature on novel ALK inhibitors.
  • Analysis of clinical data and molecular properties of emerging therapies.
  • Inclusion of studies on HSP90 inhibitors in ALK+ NSCLC.

Main Results:

  • Several potent second-generation ALK inhibitors (e.g., ceritinib, alectinib, brigatinib) are available with promising efficacy.
  • These inhibitors exhibit favorable toxicity profiles compared to earlier treatments.
  • HSP90 inhibitors also show clinical activity in ALK-positive NSCLC patients.

Conclusions:

  • New ALK inhibitors represent a significant advancement in treating advanced NSCLC.
  • These agents offer effective options for patients who have developed resistance to crizotinib.
  • Ongoing research focuses on optimizing their use and understanding resistance mechanisms.
Keywords:
ALK rearrangementNSCLCalectinibceritinibcrizotinibresistance

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