Klin Onkol 2000; 13(4): 116-121.
Summary: With fastly growing options in cancer diagnosis and therapy it is no more acceptable to select the treatment strategY jonly on the basis of histomorphology and clinical staging. Many biological features of tumors have been studied, and some of them may serve as predictors of therapeutic response enabling to tailor and hopefullylmprove the efficacy of the anti-cancer , therapy. One of these intensively studied predictive parameters, especíally in colorectal carcinoma, is thymidylate synthase j (TS). This enzyme is presentin normal andcancercells being required for regular DNA synthesis and functioning as aregulator ' of the translation. TS levels in cancer cells use to be much higher than in normal cells depending on their proliferative activity. Inhibition of TS is the principal mechanism of fluoropyrimidines and high activities of TS remarkably decreases their anticancer effect. The level of TS expression can be determined by different methods, out of which the most sensitive and practicable seems to be the polymerase chain reaction. According to determined level ofTS expression in the cells of particular malignant tumor (especially colorecta! carcinoma) it is possible to predict, with a high probability, the resistance to fluoropyrimidines, to exclude the ineffective fluoropyrimidine-based regimen from the chemotherapeutic scheme and suggest a different, potentially more effective drugs, eg. topoisomerase inhibitors etc.. In such a case the patient is not only saved from therapeutic delay caused by ineffective tretament and unnecessary toxic effects, bul offered with a rational, tumor-adjusted and presumably more effective chemotherapy.
