Circulating Tumor Cells and Lung Cancer, Utility Beyond Prognosis?

Circulating Tumour Cells and Lung Cancer, Utility Beyond Prognosis?C DiveClinical and Experimental Pharmacology Group, Cancer Research UK Manchester Institute, University of Manchester, UK. Tumour 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. An avalanche of new technology platforms for circulating tumour cell (CTC) analysis is arriving in translational research laboratories, employing different approaches to CTC enrichment, purification and molecular characterisation. The semi-automated, robust and validated CellSearch platform (Veridex) remains the only technology that is FDA approved to determine patient prognosis (in breast, prostate, and colorectal cancers) by enumeration of EpCam expressing CTCs and the ability to preserve CTCs for analysis 96h after blood draw is a major advantage for multicentre clinical trial scenarios. As yet no other CTC technology is ‘fit for purpose’ in the clinic where CTC analyses can be used in clinical decision making. Nevertheless, the impact of these new CTC technologies in understanding CTC biology and heterogeneity, and the potential for more elegant CTC based biomarkers is becoming apparent.With lung cancer as the main example, data will be presented on (i) the use of predictive and pharmacodynamic CTC based biomarkers in early clinical trial settings, (ii) the biology of CTCs with respect to epithelial to mesenchyme transition and (iii) the biological significance and composition of circulating tumour microemboli. The ability to monitor 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. I will also describe our new patient CTC derived mouse models of Small Cell Lung Cancer. The molecular profiling of single CTCs and the biological relevance of CTCs regarding intra-tumour heterogeneity will be debated.