Wilson George D, Bentzen Søren M, Harari Paul M
Department of Radiation Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
Semin Radiat Oncol. 2006 Jan;16(1):2-9. doi: 10.1016/j.semradonc.2005.08.001.
Concurrent administration of radiation and chemotherapy has emerged as a dominant form of cancer treatment. Nevertheless, our understanding of the specific mechanisms of interaction between radiation and chemotherapy is still evolving. Biological evidence gained in experimental cell lines and tumors suggests that cisplatin lesions cause repair inhibition of radiation-induced DNA damage affecting both homologous recombination and nonhomologous end joining. In the case of 5-fluorouracil (5-FU), the crucial event in the radiosensitisation process appears to be inappropriate progression through S-phase in the presence of bound drug affecting both DNA repair and cell cycle. In similar fashion, data with gemcitabine suggest that radiosensitization arises through progression into S-phase causing depletion of 2'-deoxyadenosine 5'-triphosphate pools, which leads to misincorporation and misrepair of incorrect bases in irradiated cells. As the new molecular-targeted agents become increasingly available to complement established radiation and chemoradiation treatment regimens, new concepts of drug-radiation interaction are evolving that require innovative thinking regarding the manner in which radiation and drugs cooperate and how clinical trials are best performed.
放疗和化疗的联合应用已成为癌症治疗的主要形式。然而，我们对放疗与化疗相互作用的具体机制的理解仍在不断发展。在实验细胞系和肿瘤中获得的生物学证据表明，顺铂损伤会导致辐射诱导的DNA损伤修复受到抑制，影响同源重组和非同源末端连接。就5-氟尿嘧啶（5-FU）而言，放射增敏过程中的关键事件似乎是在结合药物存在的情况下通过S期的不适当进展，这会影响DNA修复和细胞周期。同样，吉西他滨的数据表明，放射增敏是通过进入S期导致2'-脱氧腺苷5'-三磷酸池耗竭而产生的，这会导致受照射细胞中错误碱基的错误掺入和错误修复。随着越来越多的新型分子靶向药物可用于补充既定的放疗和放化疗治疗方案，药物与辐射相互作用的新概念正在不断发展，这需要在辐射与药物如何协同以及如何最好地进行临床试验方面进行创新思考。
