细胞色素P450与肿瘤的基因治疗

Cytochrome P450 and Cancer Gene Therapy

利用细胞色素P450治疗肿瘤是一种新的基因治疗方法,对提高肿瘤化疗的安全性和有效性有非常大的潜力。这种方法的首要目标就是选择性地使细胞色素P450在肿瘤细胞内超量表达。P450酶系降解的前药大部分在肿瘤内活化,提高了肿瘤细胞内药物的相对浓度,减小药物对其它组织的细胞毒性。本文概述了可被细胞色素P450降解的用于肿瘤治疗的前药以及重组细胞色素P450在基因治疗中的应用。

Cytochrome P450-based gene therapy is a novel prodrug activation strategy for cancer treatment that has substantial potential for improving the safety and efficacy of cancer chemotherapies. The primary goal of the strategy is to selectively increase tumor cell exposure to cytotoxic drug metabolites generated locally by a prodrug-activating P450 enzyme, which expresses highly in tumor cells after being transduced. This leads to more efficient killing of the transduced tumor cells without a significant increase in host toxicity. The article reviews the prodrug that can be metabolited by cytochrome P450 and the application of gene-engineered P450 in cancer gene therapy.