Affiliation: Department of Physiology and Pharmacology, Campus Miguel de Unamuno E.I.D. S-09, 37007- Salamanca, Spain.
Gastrointestinal tumours constitute one of the worldwide leading causes of death. One important limitation in the battle against these types of cancer is their lack of sensitivity to currently available chemotherapy and the development of drug resistance during treatment. The mechanisms responsible for this refractivity include a reduction in drug uptake, enhanced drug export, intracellular inactivation of the effective agent, alteration of the molecular target, an increase in the activity of the target route to be inhibited or the appearance or stimulation of alternative routes, enhanced repair of drug-induced modification in the target molecules, and activation/inhibition of intracellular signalling pathways, which leads to a negative balance between apoptosis/survival of tumour cells. A better understanding of these mechanisms is needed in order to develop both accurate tests to predict the lack of response to chemotherapy and novel approaches aimed to overcome the drug resistance of gastrointestinal tumours. The complexity of this issue is further increased owing to the existence of marked differences among the types of primary malignant gastrointestinal tumours and the diversity of tissues from which metastatic cells can access the gut. Moreover, inter-individual variability plus the fact that sensitivity/refractivity may change during the evolution of the tumour further complicate the overall situation. The present article reviews anti-cancer agents used either alone or, more frequently, combined in regimens, as neoadjuvant or postsurgical adjuvant chemotherapy within the context of the available curative and palliative therapeutic options used to treat the most common types of cancer of the gastrointestinal tract and pancreas.