Integrating quantitative and qualitative studies on circulating tumor cells (CTC) in early clinical trials. (a) Schematic representation of how studying CTCs at different time-points during the treatment can provide information on drug effects (PD studies), discover mechanisms of resistance and also assess changes in CTC counts as predictive markers of responses. (b) Changes in CTC counts compared with baseline enumeration in patients participating in the phase I trial of the c-MET inhibitor ARQ-197. PD, pharmacodynamics. (Reprinted with permission from  Yap TA et al. J Clin Oncol 2011, 29:1271-1279. (Copyright by American Society of Clinical Oncology. All rights reserved).