Personalized medicine in oncology: where have we come from and where are we going?

Current advances in the biology of cancer and emergence of new tools for genome analysis have opened clinical perspectives in oncology, generally termed as 'personalized medicine'. This broad term must encompass previous well-proven strategies, such as pharmacogenetics- and pharmacokinetics-based dosing, with more recently introduced pharmacogenomics approaches, all applied as a means to tailor treatment to a given patient presenting with a given tumor. Despite outstanding results in lung cancer, colorectal cancer and melanoma, only a few predictive biomarkers are currently justified in routine clinical practice. Overall, there is a persistent gap between the growing number of identified deregulated pathways or genetic mutations, both at the tumor and the constitutional levels, and their actual implementation at the bedside as part of clinical routine. This article underlines these limitations and covers several issues that may explain the discrepancy between the plethora of published data about emerging biomarkers, and the relative scarcity of tests eventually reaching a clinically validated application. The main identified difficulties concern invasive and costly prospective biomarker studies and the issue of tumor heterogeneity. Finally, early trial designs for targeted therapies as well as those for conventional cytotoxics may not necessarily address the right questions by skipping critical end points. Proposed solutions point out the use of liquid biopsies and systems biology approaches, for an easier implementation of personalized medicine at the bedside.