Clinical implications of 5-FU modulation

In recent years, due to the advent of sensitive instrumentation and methodo logies, it has been possible to identify, parameters that predict the (qual ity of response of individual patients to treatments for specific selected diseases, eg, colon carcinoma and breast carcinoma. Ongoing studies are att empting to identify sensitive patients in ol der to select treatment regime ns suitable for the individual patient. The critical question that remains is whether the basis for drug resistance is due in part to insufficient del ivery of drugs to target tumor cells or to the resistance of target tumor c ells by various mechanisms, including, in the case of 5-fluorouracil (5-FU) drug transport, metabolism, expression of the target enzyme thymidylate sy nthase (dTMPS), depletion of folate cofactors, and/or level of competing su bstrate deoxyuridine monophosphate,Also in recent years, attempts have been made to delineate mechanisms of resistance to the fluoropyrimidines. On th e basis of such studies, it may be possible to develop approaches aimed at the selective modulation of the therapeutic efficacy of these agents in tre mor tissues with varying degrees of sensitivity to fluoropyrimidines, eg, p atients with advanced colorectal cancer One such approach is the use of cal cium folinate to modulate the therapeutic efficacy of 5-FU.