Molecular Testing Challenges in Advanced NSCLC: From EGFR to PDL1 and Beyond
This Lancet review addresses the practical challenges of molecular testing in non-small-cell lung cancer, where an expanding panel of actionable targets must be assessed from increasingly small biopsy specimens. The authors discuss tumor heterogeneity, resistance-driven clonal evolution requiring repeat sampling, and the growing role of NGS platforms that test multiple variants simultaneously. The UK Stratified Medicine Programme and National Lung Matrix Trial are presented as models for NGS-guided molecularly stratified clinical trials.
The original study
Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease.
- Authors
- Hiley CT, Le Quesne J, Santis G, Sharpe R, de Castro DG, Middleton G, et al.
- Journal
- Lancet (London, England)
- Type
- Journal Article, Research Support, Non-U.S. Gov't, Review
- PMID
- 27598680
Original 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.