Kinase activation in circulating cells: Opportunities for biomarkers for diagnosis and therapeutic monitoring

A clinically useful tool to assay phosphorylation-dependent signaling in circulating cells has the potential to provide a wealth of information about a patient's health, including information unavailable by any other method. Patterns of kinase activation, such as the abnormal signaling characteristic of myeloproliferative disorders, may offer highly specific biomarkers for diagnosis or monitoring the efficacy of therapeutics. For assays of kinase activity in circulating leukocytes to be standardized, let alone made practical for the clinic, numerous technical hurdles must be overcome. In this review the current status of analysis of kinase signaling in circulating cells and recent progress in biomarker discovery and validation is discussed. Looking forward, the potential value of signaling patterns as complex biomarkers and the resulting need for future development of robust, multiplexed assays of kinase activation is addressed.