The molecular biology of colorectal cancer development and the associated genetic events

Colorectal carcinoma remains the second most common malignancy in the western world. Mortality has remained stable despite advances in surgical and adjuvant radio- and chemotherapy regimens. This has renewed interest in the understanding of the basic principles of the molecular biology of colorectal carcinogenesis. The condition is characterised by multiple mutations in common oncogenes and tumour suppressor genes encompassing the inherited conditions familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer. The latter is characterised by genomic instability due to mismatch repair gene defects. These conditions and the role of the tumour protease systems, e.g. the plasminogen activation system and the matrix metalloproteinases, involved in the degradation of the extracellular matrix, provide an ideal role model for the study of carcinogenesis. The understanding and future application of these basic mechanisms, combined with the recent innovative work on the potential prophylactic role of COX2 inhibition, may provide further insight in the ultimate quest for a 'cure'. In the long-term, this concept may have to be achieved at the molecular level.