Department of Cell Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Future Oncol. 2009 Dec;5(10):1685-704. doi: 10.2217/fon.09.127.
Most of the anticancer chemotherapeutic drugs that are broadly and successfully used today are DNA-damaging agents. Targeting of DNA has been proven to cause relatively potent and selective destruction of tumor cells. However, the clinical potential of DNA-damaging agents is limited by the adverse side effects and increased risk of secondary cancers that are consequences of the agents' genotoxicity. In this review, we present evidence that those agents capable of targeting DNA without inducing DNA damage would not be limited in these ways, and may be as potent as DNA-damaging agents in the killing of tumor cells. We use as an example literature data and our own research of the well-known antimalarial drug quinacrine, which binds to DNA without inducing DNA damage, yet modulates a number of cellular pathways that impact tumor cell survival.
目前广泛应用且疗效显著的大多数抗癌化疗药物都是 DNA 损伤剂。靶向 DNA 已被证明可导致肿瘤细胞相对有效且具有选择性的破坏。然而，DNA 损伤剂的临床应用潜力受到其遗传毒性导致的不良反应和继发性癌症风险增加的限制。在本综述中，我们提供的证据表明，那些能够靶向 DNA 而不诱导 DNA 损伤的药物不会受到这些限制，并且在杀伤肿瘤细胞方面可能与 DNA 损伤剂一样有效。我们以著名的抗疟药奎宁为例，其与 DNA 结合而不诱导 DNA 损伤，但可调节影响肿瘤细胞存活的许多细胞通路。我们使用文献数据和我们自己的研究作为例证。
