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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer

Published on: September 8, 2023

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Treating patients with ALK-positive non-small cell lung cancer: latest evidence and management strategy

Bin-Chi Liao1, Chia-Chi Lin2, Jin-Yuan Shih3

  • 1Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.

Therapeutic Advances in Medical Oncology
|September 2, 2015
PubMed

Insights

Anaplastic lymphoma kinase (ALK) gene rearrangements in non-small cell lung cancer (NSCLC) are targeted by inhibitors like crizotinib. Newer therapies, including second-generation ALK inhibitors and Hsp90 inhibitors, are being developed to overcome resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Anaplastic lymphoma kinase (ALK) gene rearrangements, often with echinoderm microtubule-associated protein-like 4 (EML4), are identified in a subset of non-small cell lung cancer (NSCLC) patients.
  • The diagnostic test for EML4-ALK rearrangement is fluorescence in situ hybridization.
  • Crizotinib, an FDA-approved ALK inhibitor, demonstrated efficacy in advanced ALK-positive NSCLC since 2011.

Purpose of the Study:

  • To review recent advancements in ALK inhibitors and Heat shock protein 90 (Hsp90) inhibitors for treating advanced ALK-positive NSCLC.
  • To discuss emerging resistance mechanisms to ALK inhibitors.
  • To explore management strategies for advanced ALK-positive NSCLC.

Main Methods:

  • Review of recent literature on ALK inhibitors (crizotinib, ceritinib, alectinib) and Hsp90 inhibitors.
  • Analysis of mechanisms of acquired resistance to crizotinib.
  • Discussion of therapeutic strategies for advanced ALK-positive NSCLC.

Main Results:

  • Second-generation ALK inhibitors (ceritinib, alectinib) were developed to overcome resistance to crizotinib.
  • Hsp90 inhibitors have shown activity in ALK-positive NSCLC.
  • Various resistance mechanisms to crizotinib have been identified.

Conclusions:

  • Second-generation ALK inhibitors and Hsp90 inhibitors represent significant progress in treating advanced ALK-positive NSCLC.
  • Understanding resistance mechanisms is crucial for developing effective management strategies.
  • Continued research into novel inhibitors and treatment approaches is essential for improving patient outcomes.
Keywords:
EML4–ALK rearrangementalectinibceritinibcrizotinibheat shock protein 90 inhibitornon-small cell lung cancer

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