From the Drug Development Unit, Royal Marsden Hospital, Sutton, Surrey, United Kingdom
Authors' disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Johann S. de Bono, MD, PhD, MSc, FRCP, Senior Lecturer and Honorary Consultant, Cancer Research, United Kingdom Centre for Cancer Therapeutics, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Downs Road, Sutton, Surrey, SM2 5PT; e-mail: johann.de-bono{at}icr.ac.uk
Overview: Biomarkers are objectively measured indicators of normal biologic or pathogenic processes, or of pharmacologic responses to therapeutic intervention. The use of analytically validated and clinically qualified biomarkers could potentially accelerate and facilitate anticancer drug development, which remains slow, costly, and inefficient. Despite this potential for improvement, only a fraction of early clinical trials evaluating anticancer drugs involve a biomarker. Moreover, many of the biomarkers evaluated to date have been exploratory and have not been validated or qualified, making it difficult to draw significant conclusions from their use. The enumeration of circulating tumor cells (CTCs) in the blood of patients with cancer is a promising, analytically validated, and clinically qualified biomarker that merits detailed evaluation in anticancer drug development. Pretreatment CTC counts robustly predict overall survival in several common cancers and have potential as stratification factors in randomized trials. Post-treatment CTC counts may predict overall survival after treatment and could be used as an efficacy endpoint. Furthermore, molecular characterization of CTC by fluorescence in situ hybridization (FISH) or immunofluorescence may play a role in pretreatment patient selection and as a pharmacodynamic marker. Further evaluation of CTC is warranted in carefully designed clinical trials.