Challenges in molecular testing in non-small-cell lung cancer patients with advanced disease.
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.
Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK; Division of Cancer Studies, King's College London, London, UK.
Crispin T
CT
Hiley
Department of Cancer Studies, University of Leicester, Leicester, UK.
John
J
Le Quesne
Department of Respiratory Medicine and Allergy, King's College London, UK.
George
G
Santis
Cancer Research UK, London, UK.
Rowena
R
Sharpe
Centre for Molecular Pathology, Royal Marsden Hospital, Sutton, UK; School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast, UK.
David Gonzalez
DG
de Castro
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK; University Hospital Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK.
Gary
G
Middleton
Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, UK; CRUK Lung Cancer Centre of Excellence, UCL Cancer Institute, London, UK. Electronic address: charles.swanton@crick.ac.uk.
Charles
C
Swanton
D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012720:Severity of Illness Index
D014408:Biomarkers, Tumor; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases