Colorectal carcinoma remains the second most common malignancy in the weste
rn world. Mortality has remained stable despite advances in surgical and ad
juvant radio- and chemotherapy regimens. This has renewed interest in the u
nderstanding of the basic principles of the molecular biology of colorectal
carcinogenesis. The condition is characterised by multiple mutations in co
mmon oncogenes and tumour suppressor genes encompassing the inherited condi
tions 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 metalloprote
inases, involved in the degradation of the extracellular matrix, provide an
ideal role model for the study of carcinogenesis. The understanding and fu
ture application of these basic mechanisms, combined with the recent innova
tive 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.