Cancer Research UK Drug-DNA Interactions Research Group, UCL Cancer Institute, London WC1E 6BT, UK.
Curr Opin Pharmacol. 2012 Aug;12(4):398-402. doi: 10.1016/j.coph.2012.03.008. Epub 2012 Apr 11.
DNA-targeted chemotherapies remain fundamental in clinical management of both common solid tumours and hematologic malignancies. Recent studies indicate that novel combinations of cytotoxic chemotherapy may have significant activity even in tumours regarded as being resistant to conventional chemotherapy. In addition, the search for more selective and efficacious drugs that can deliver critical DNA damage with minimal side effects continues. Trabectedin, bendamustine and the pyrrolobenzodiazepine dimer SG2000 exemplify three different classes of DNA targeted agent undergoing clinical evaluation. Increasingly, DNA damaging drugs are being used in combination with novel agents such as small molecule inhibitors or antibodies targeting receptor tyrosine kinases. Understanding the mechanistic basis for interactions of these novel targeted agents with DNA-interactive drugs will inform design of optimal combinations for future studies and is critical to maximize benefit in the clinic.
DNA 靶向化疗在常见实体瘤和血液恶性肿瘤的临床治疗中仍然是基础。最近的研究表明，即使是被认为对传统化疗有耐药性的肿瘤，新型细胞毒性化疗药物联合治疗也可能具有显著的活性。此外，人们仍在继续寻找更具选择性和疗效的药物，这些药物可以在最小副作用的情况下传递关键的 DNA 损伤。 trabectedin、bendamustine 和吡咯并苯并二氮杂䓬二聚体 SG2000 就是正在进行临床评估的三种不同类型的 DNA 靶向药物的代表。越来越多的 DNA 损伤药物与新型药物联合使用，如针对受体酪氨酸激酶的小分子抑制剂或抗体。了解这些新型靶向药物与 DNA 相互作用药物相互作用的机制基础，将为未来研究设计最佳联合治疗方案提供信息，并对最大限度地提高临床获益至关重要。
