Molecular analysis of circulating tumour cells-biology and biomarkers.
Growing evidence for intratumour heterogeneity informs us that single-site biopsies fall short of revealing the complete genomic landscape of a tumour. With an expanding repertoire of targeted agents entering the clinic, screening tumours for genomic aberrations is increasingly important, as is interrogating the tumours for resistance mechanisms upon disease progression. Multiple biopsies separated spatially and temporally are impractical, uncomfortable for the patient and not without risk. Here, we describe how circulating tumour cells (CTCs), captured from a minimally invasive blood test-and readily amenable to serial sampling-have the potential to inform intratumour heterogeneity and tumour evolution, although it remains to be determined how useful this will be in the clinic. Technologies for detecting and isolating CTCs include the validated CellSearch(®) system, but other technologies are gaining prominence. We also discuss how recent CTC discoveries map to mechanisms of haematological spread, previously described in preclinical models, including evidence for epithelial-mesenchymal transition, collective cell migration and cells with tumour-initiating capacity within the circulation. Advances in single-cell molecular analysis are enhancing our ability to explore mechanisms of metastasis, and the combination of CTC and cell-free DNA assays are anticipated to provide invaluable blood-borne biomarkers for real-time patient monitoring and treatment stratification.
Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, 550 Wilmslow Road, Manchester M20 4BX, UK.
Matthew G
MG
Krebs
Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, 550 Wilmslow Road, Manchester M20 4BX, UK.
Robert L
RL
Metcalf
Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, 550 Wilmslow Road, Manchester M20 4BX, UK.
Louise
L
Carter
Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, 550 Wilmslow Road, Manchester M20 4BX, UK.
Ged
G
Brady
Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, 550 Wilmslow Road, Manchester M20 4BX, UK.
Fiona H
FH
Blackhall
Clinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester and Manchester Cancer Research Centre, 550 Wilmslow Road, Manchester M20 4BX, UK.
Caroline
C
Dive
D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D018450:Disease Progression; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D057285:Precision Medicine / Q000379:methods
D014408:Biomarkers, Tumor