Zentralinstitut für Laboratoriumsmedizin und Pathobiochemie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany.
Mini Rev Med Chem. 2010 Sep;10(10):887-904. doi: 10.2174/138955710792007196.
The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview on the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial- (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs.
癌症的治愈仍然是医学领域的一个巨大挑战。长期以来，手术、化疗和放疗等方法在许多情况下都取得了成功；然而，侵袭性、转移性和难以到达的肿瘤仍然是一个未解决的持续问题。在过去的三十年中，作为治疗棘手癌症的一种替代方法，已经开发出了旨在定位、检测和特异性杀伤肿瘤细胞的靶向治疗方法。这些治疗方法中的大多数要么基于抗体依赖性细胞毒性，要么基于靶向递送细胞毒性药物，要么基于肿瘤部位特异性激活前药。后者是一个两步过程。在第一步中，通过将酶或其基因引导至肿瘤细胞，将选定的酶积聚在肿瘤中。在第二步中，应用一种无害的前药，仅在肿瘤部位由该酶特异性转化为细胞毒性药物。自 1974 年首次提出该概念以来，已经对许多靶向系统、酶和前药进行了研究和改进。这篇综述简要概述了癌症治疗中靶向治疗的历史和最新进展。我们涵盖了相关技术，如抗体导向酶前药疗法（ADEPT）、基因导向酶前药疗法（GDEPT）以及相关疗法，如梭菌（CDEPT）和聚合物导向酶前药疗法（PDEPT），重点介绍了前药转化酶、前药和药物。
