Diagnosis and Treatment of ALK Aberrations in Metastatic NSCLC

Curr Treat Options Oncol. 2019 Sep 4;20(10):79. doi: 10.1007/s11864-019-0675-9.

Abstract

There has been rapid progress in the use of targeted therapies for ALK-positive which has led to improve dramatically PFS and OS in the metastatic ALK-rearranged NSCLC patients. There are several molecules now available (crizotinib, ceritinib, brigatinib, alectinib, and lorlatinib) and others in development. Such an improvement in treatment efficacy has even more highlighted the importance of an adequate identification of ALK alterations. Efficient and easily accessible testing tools are required to identify eligible patients in a timely fashion. Different methods for detecting ALK+ NSCLC patients are now available, with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) currently representing validated diagnostic techniques for the initial assessment of ALK status. Furthermore the widespread use of next-generation sequencing to detect other possible different activating mutations has allowed to identify individual ALK fusion variants. Several more expensive and time-consuming methods are also available nowadays which have the advantage to detect even rarer uncommon ALK fusion variants and mutations in tumour or blood samples. A review of the evolving testing-treatment landscape is needed to highlight the importance of properly diagnosing and treating this group of patients.

Keywords: ALK aberration; NSCLC; Testing.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase / antagonists & inhibitors
  • Anaplastic Lymphoma Kinase / genetics*
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / etiology*
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Chromosome Aberrations*
  • Disease Management
  • Humans
  • Liquid Biopsy / methods
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / etiology*
  • Lung Neoplasms / therapy*
  • Molecular Diagnostic Techniques
  • Molecular Targeted Therapy / methods
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use

Substances

  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • ALK protein, human
  • Anaplastic Lymphoma Kinase