Abstract

Tissue biopsies are clearly the gold standard with which to interrogate a patient’s tumour biology and assess biomarkers useful for treatment decision making. However, for longitudinal monitoring of disease in certain cancer types (e.g. lung and pancreas and particularly in patients with multiple metastatic lesions), serial biopsies may not be readily acquired and easily repeatable and a less invasive tumour sample is required. With lung cancer as the main example, this seminar will explore the technology platforms for CTC analysis, the prognostic significance of CTC number, and the potential in early clinical trial settings for CTC assays of predictive biomarkers and for demonstrating proof of drug mechanism and concept. The possibility to examine tumour evolution from a drug sensitive to drug resistant phenotypes via CTC analysis will be discussed given the current paradigms of response followed by relapsed witnessed for several targeted therapeutics. The biology of CTCs with respect to epithelial to mesenchyme transition together with the relevance and composition of circulating tumour microemboli will be also be addressed. Finally, the horizon of profiling CTCs will be touched upon and the biological relevance of CTCs regarding intra-tumour heterogeneity will be debated.