Related Experiment Video

Updated: Jan 20, 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

354

How I treat ALK-positive non-small cell lung cancer

Michael G McCusker1, Alessandro Russo2, Katherine A Scilla1

  • 1University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, Maryland, USA.

ESMO Open
|August 20, 2019
PubMed

Insights

Anaplastic Lymphoma Kinase (ALK) rearrangement in non-small cell lung cancer (NSCLC) presents complex treatment challenges. This study provides an evidence-based algorithm to guide diagnosis, TKI selection, resistance management, and CNS disease control for ALK-positive NSCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Anaplastic Lymphoma Kinase (ALK) rearrangement is a key driver in a subset of non-small cell lung cancer (NSCLC).
  • The development of ALK tyrosine kinase inhibitors (TKIs) has revolutionized treatment, but resistance mechanisms and central nervous system (CNS) disease pose significant challenges.
  • Molecular testing is crucial for identifying ALK rearrangements and resistance mutations to guide therapy.

Purpose of the Study:

  • To address complex clinical questions regarding the diagnosis and management of ALK-rearranged NSCLC.
  • To provide evidence-based guidance on selecting first-line ALK TKIs and managing treatment resistance.
  • To propose a therapeutic algorithm for optimizing patient care and outcomes in ALK-positive NSCLC.

Main Methods:

  • Comprehensive review and evidence-based interpretation of existing studies on ALK-rearranged NSCLC.
  • Integration of clinical experience from the authors' institution.
  • Development of a therapeutic algorithm based on current evidence and clinical practice.

Main Results:

  • Molecular testing identifies ALK rearrangement and common resistance mechanisms, informing treatment decisions.
  • Effective strategies exist for managing CNS disease and overcoming ALK TKI resistance.
  • A proposed algorithm offers a structured approach to the multifaceted management of ALK-positive NSCLC.

Conclusions:

  • ALK-rearranged NSCLC requires a nuanced management strategy due to evolving resistance patterns and CNS involvement.
  • Molecular diagnostics play a pivotal role in guiding personalized treatment selection and adaptation.
  • The proposed therapeutic algorithm aims to standardize and improve clinical decision-making for ALK-positive NSCLC patients globally.
Keywords:
ALKNSCLCacquired resistancealectinibceritinibcrizotiniblorlatinib

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