Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease

Lancet. 2016 Sep 3;388(10048):1002-11. doi: 10.1016/S0140-6736(16)31340-X. Epub 2016 Sep 1.

Abstract

Lung cancer diagnostics have progressed greatly in the previous decade. Development of molecular testing to identify an increasing number of potentially clinically actionable genetic variants, using smaller samples obtained via minimally invasive techniques, is a huge challenge. Tumour heterogeneity and cancer evolution in response to therapy means that repeat biopsies or circulating biomarkers are likely to be increasingly useful to adapt treatment as resistance develops. We highlight some of the current challenges faced in clinical practice for molecular testing of EGFR, ALK, and new biomarkers such as PDL1. Implementation of next generation sequencing platforms for molecular diagnostics in non-small-cell lung cancer is increasingly common, allowing testing of multiple genetic variants from a single sample. The use of next generation sequencing to recruit for molecularly stratified clinical trials is discussed in the context of the UK Stratified Medicine Programme and The UK National Lung Matrix Trial.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • ErbB Receptors / analysis
  • ErbB Receptors / genetics
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Mutation
  • Receptor Protein-Tyrosine Kinases / genetics
  • Severity of Illness Index

Substances

  • Biomarkers, Tumor
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases