Research Group Reprogramming, REBIRTH Cluster of Excellence, Hannover Medical School, Hannover, Germany.
Neoplasia. 2013 Mar;15(3):239-48. doi: 10.1593/neo.121954.
Gene transfer of drug resistance (CTX-R) genes can be used to protect the hematopoietic system from the toxicity of anticancer chemotherapy and this concept recently has been proven by overexpression of a mutant O(6)-methylguaninemethyltransferase in the hematopoietic system of glioblastoma patients treated with temozolomide. Given its protection capacity against such relevant drugs as cytosine arabinoside (ara-C), gemcitabine, decitabine, or azacytidine and the highly hematopoiesis-specific toxicity profile of several of these agents, cytidine deaminase (CDD) represents another interesting candidate CTX-R gene and our group recently has established the myeloprotective capacity of CDD gene transfer in a number of murine transplant studies. Clinically, CDD overexpression appears particularly suited to optimize treatment strategies for acute leukemias and myelodysplasias given the efficacy of ara-C (and to a lesser degree decitabine and azacytidine) in these disease entities. This article will review the current state of the art with regard to CDD gene transfer and point out potential scenarios for a clinical application of this strategy. In addition, risks and potential side effects associated with this approach as well as strategies to overcome these problems will be highlighted.
基因转移耐药（CTX-R）基因可用于保护造血系统免受抗癌化疗的毒性，这一概念最近已通过在接受替莫唑胺治疗的胶质母细胞瘤患者的造血系统中过度表达突变的 O(6)-甲基鸟嘌呤甲基转移酶得到证实。鉴于其对阿糖胞苷（ara-C）、吉西他滨、地西他滨或阿扎胞苷等相关药物的保护能力，以及这些药物中几种药物的高度造血特异性毒性特征，胞苷脱氨酶（CDD）代表另一种有趣的候选 CTX-R 基因，我们的小组最近在多项小鼠移植研究中证实了 CDD 基因转移的骨髓保护能力。在临床上，鉴于 ara-C（以及在较小程度上 decitabine 和 azacytidine）在这些疾病实体中的疗效，CDD 过表达似乎特别适合优化急性白血病和骨髓增生异常的治疗策略。本文将回顾 CDD 基因转移的最新技术现状，并指出该策略临床应用的潜在方案。此外，还将强调与该方法相关的风险和潜在副作用，以及克服这些问题的策略。
