Challenges in Development and Validation of Surrogate and Predictive Markers

Molecular heterogeneity exists even within tumors derived from the same tissue of origin, and clinical benefit associated with any drug is typically limited to a subset of patients. This aspect of cancer and cancer therapy remains the most challenging, even in the current era of “targeted therapy,” which is characterized by a move from the empiric approach of “one size fits all” to personalized therapy (1). The missing link for achieving this goal is the availability of robust and validated predictive biomarkers endowed with the discriminating power to identify those individuals who will derive benefit from a particular targeted therapy from those who will not. The model of preoperative systemic therapy is a powerful tool for studies aiming to discover and validate surrogate biomarkers.