Harold H.J. Backus, Youcef M. Rustum, Cornelius J. van Groeningen, Godefridus J. Peters

Colorectal cancer is one of the most common malignancies in Western nations. Treatment with 5-fluorouracil and leucovorin resulting in inhibition of DNA synthesis after inhibition of thymidylate synthase is the most common strategy for adjuvant and systemic chemotherapy in this disease. However, the majority of patients still fail to respond to this combination; therefore, new chemotherapeutic strategies have been developed. This process has proceeded rapidly due to a more proper translation of preclinical results to the clinic. Knowledge of proximal parameters (drug activation, drug-target interaction) and distal parameters (cell growth inhibitory parameters and cell death parameters) in drug response should offer the opportunity to discriminate between sensitivity and resistance to chemotherapy and therapeutic selectivity. This clinical commentary presents a review of a symposium held at the Vrije Universiteit Medical Center, Amsterdam, The Netherlands, which focused on both the preclinical and clinical aspects relating to the treatment of colorectal cancer.