卡培他滨作用机制耐药及逆转讲义.pptVIP

卡培他滨作用机制耐药及逆转 卡培他滨的作用机制 肿瘤组织5-FU的浓度获得了特异性的提高 Schuller J et al.Cancer Chemother Pharmacol 2000;45:291-297 抗肿瘤活性 毒性 卡培他滨直接提高肿瘤细胞内浓度 TP DPD OPRT 降解 卡培他滨可能的耐药机制---药物外排或DNA修复 Epigenetic mechanisms affecting cancer cell chemosensitivity. Chemotherapy agents are often pro-drugs, which can be activated or inactivated by specific cellular enzymes. Active metabolites penetrate the nucleus and induce DNA damage, cell cycle arrest and apoptosis. ABC transporters mediate drug efflux, thereby protecting cancer cells. ABCB1, ABCG2, UGT1A1, TP, MGMT, p16 and