Chemoradiotherapy - mechanism of increased cytostatics activation during the post-radiation reaction
Abstract
Chemoradiotherapy employing nucleoside analogues, esp. fluorinated pyrimidines became a standard treatment approach in a variety of malignant tumours. Its mechanism of effect has not been discovered in detail.
The introduction of capecitabine initiated a detailed investigation of the original concept of enhanced pyrimidine activation to active forms caused by an induction of pyrimidine metabolizing enzymes in a scope of a post-radiation reaction. A wide spectrum of cytokines and enzymes is induced by an irradiation including metabolic enzymes - thymidine phosphorylase (TP), thymidine kinase (TK), dihydropyrimidine dehydrogenase (DPD), thymidylate synthetase (TS), deoxycytidine kinase (dCK), deoxycytidine monophosphate kinase (dCMPK) and deoxycytidine deaminase (dCyD).
These enzymes metabolize pyrimidine nucleoside analogues - 5-fluorouracil, capecitabine, ara-C and gemcitabine. Either an enhanced transcription of the relevant mRNA or an increased protein content or both had been found in irradiated cells.