Tailored therapy of colorectal cancer: results, challenges and future directions.

Colorectal cancer is a leading cause of cancer mortality and morbidity. Despite the recent results of systemic chemotherapy, more than 40% of patients with advanced cancer still do not achieve substantial benefits with cytotoxic agents. Therefore, new tailored strategies are warranted to improve the probability of disease control. The rationale for this approach is based on the identification of the in vivo interactions among patient's characteristics, disease physiopathology, and drug pharmacodynamics and pharmacokinetics. Genomic and proteomic technologies may clarify the mechanisms involved in cancer growth and progression in each single patient and in the molecular basis of interindividual differences of anticancer drugs in terms of efficacy and toxicity. Despite the recent encouraging data, the clinical use of targeted therapy is hampered by several questions, such as: optimal biologic dose and schedule, lack of predictive surrogate biomarkers, and modalities of combination with chemotherapy/radiotherapy. Further efforts are needed to improve the reliability of genomic and proteomic technologies, in particular regarding their standardization and widespread availability. These unsolved issues make tailored therapy an open challenge.