Related Experiment Video

Updated: Feb 9, 2026

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
05:17

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing

Published on: October 10, 2025

421

Treating ALK-positive non-small cell lung cancer

Dimitrios C Ziogas1, Anna Tsiara1, Georgios Tsironis1

  • 1Department of Clinical Therapeutics, Alexandra General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.

Annals of Translational Medicine
|June 5, 2018
PubMed

Insights

Targeted therapies like ALK inhibitors have transformed non-small cell lung cancer (NSCLC) treatment. Newer agents show improved efficacy over crizotinib, especially for brain metastases, though optimal sequencing is still debated.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Genomic alterations, including EGFR mutations and ALK rearrangements, are key drivers in non-small cell lung cancer (NSCLC).
  • ALK rearrangements have led to the development of targeted therapies, specifically ALK tyrosine kinase inhibitors (TKIs), revolutionizing personalized NSCLC treatment.
  • Crizotinib, the first ALK TKI, demonstrated superiority over chemotherapy but faced challenges with acquired resistance and limited central nervous system (CNS) efficacy.

Purpose of the Study:

  • To review the current understanding of ALK-positive NSCLC biology.
  • To discuss the landscape of available ALK tyrosine kinase inhibitors (TKIs) for NSCLC treatment.
  • To examine clinical practice issues and optimal sequencing strategies for ALK inhibitors in NSCLC.

Main Methods:

  • Review of published literature on ALK-positive NSCLC.
  • Analysis of clinical trial data for approved and investigational ALK inhibitors.
  • Discussion of resistance mechanisms and CNS efficacy of ALK TKIs.

Main Results:

  • Four ALK TKIs (crizotinib, ceritinib, alectinib, brigatinib) are FDA/EMA approved, with more agents under investigation.
  • Recent Phase III trials indicate superior efficacy of alectinib compared to crizotinib in the first-line setting for ALK-rearranged NSCLC.
  • Alectinib demonstrates significant efficacy even in patients with CNS involvement, addressing a key limitation of earlier TKIs.

Conclusions:

  • ALK inhibitors represent a significant advancement in personalized medicine for NSCLC.
  • Novel ALK TKIs offer improved potency and CNS penetration compared to crizotinib.
  • Optimal frontline treatment selection and sequencing of ALK inhibitors remain critical considerations for maximizing patient outcomes in ALK-positive NSCLC.
Keywords:
Anaplastic lymphoma kinase (ALK) rearrangementsalectinibbrigatinibceritinibcrizotinibnon-small cell lung cancer (NSCLC)resistancetyrosine kinase inhibitors (TKI)

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