Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki 305-8566, Japan.
Int J Mol Sci. 2021 Mar 19;22(6):3140. doi: 10.3390/ijms22063140.
Chemo-radiotherapy, which combines chemotherapy with radiotherapy, has been clinically practiced since the 1970s, and various anticancer drugs have been shown to have a synergistic effect when used in combination with radiotherapy. In particular, cisplatin (CDDP), which is often the cornerstone of multi-drug combination cancer therapies, is highly versatile and frequently used in combination with radiotherapy for the treatment of many cancers. Therefore, the mechanisms underlying the synergistic effect of CDDP and radiotherapy have been widely investigated, although no definitive conclusions have been reached. We present a review of the combined use of CDDP and radiotherapy, including the latest findings, and propose a mechanism that could explain their synergistic effects. Our hypothesis involves the concepts of overlap and complementation. "Overlap" refers to the overlapping reactions of CDDP and radiation-induced excessive oxidative loading, which lead to accumulating damage to cell components, mostly within the cytoplasm. "Complementation" refers to the complementary functions of CDDP and radiation that lead to DNA damage, primarily in the nucleus. In fact, the two concepts are inseparable, but conceptualizing them separately will help us understand the mechanism underlying the synergism between radiation therapy and other anticancer drugs, and help us to design future radiosensitizers.
化疗-放疗联合治疗，结合了化疗和放疗，自 20 世纪 70 年代以来已经在临床上得到应用，并且已经证明各种抗癌药物与放疗联合使用时具有协同作用。特别是顺铂（CDDP），它经常是多药联合癌症治疗的基石，具有很高的多功能性，并且经常与放疗联合用于治疗许多癌症。因此，CDDP 和放疗协同作用的机制已经被广泛研究，尽管还没有得出明确的结论。我们介绍了 CDDP 和放疗的联合应用，包括最新的发现，并提出了一个可以解释它们协同作用的机制。我们的假设涉及重叠和互补的概念。“重叠”是指 CDDP 和辐射诱导的过度氧化负荷的重叠反应，导致细胞成分的积累性损伤，主要在细胞质内。“互补”是指 CDDP 和辐射的互补功能，导致 DNA 损伤，主要在核内。事实上，这两个概念是不可分割的，但将它们分开概念化将有助于我们理解放疗与其他抗癌药物协同作用的机制，并帮助我们设计未来的放射增敏剂。
