Molecularly targeted cancer therapy: some lessons from the past decade

• Tumor heterogeneity is the key factor underlying limited response rate to targeted therapy.
• Personalized medicines depend on biomarkers for selecting patients and directing therapy.
• Co-development of predictive and response biomarkers is required for drug development.
• PDX model-based trials mimicking human patients may improve biomarker discovery.

The tremendous advances achieved in the understanding of cancer biology have delivered unprecedented progress in molecularly targeted cancer therapy in the past decade. The fast growing category of targeted anticancer agents available for clinical use is accompanied by a conceptual revolution in anticancer drug development. Nevertheless, molecularly targeted cancer therapy remains challenged by a high failure rate and an extremely small proportion of patients that can benefit. It is pivotal to take lessons from the past and seek new solutions. This review discusses conceptual progress and remaining challenges in molecularly targeted cancer therapy, and proposes feasible alternatives to increase chances of clinical success in the future.