Why concurrent cddp and radiotherapy has synergistic antitumor effects: A review of in vitro experimental and clinical-based studies

Shinsuke Nagasawa, Junko Takahashi, Gen Suzuki, Yamazaki Hideya, Kei Yamada

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish
Article number3140
Pages (from-to)1-13
Number of pages13
JournalInternational journal of molecular sciences
Volume22
Issue number6
DOIs
Publication statusPublished - 2021 Mar 2
Externally publishedYes

Keywords

  • Chemo-radiotherapy (CRT)
  • Cis-diamminedichloroplatinum (cisplatin: CDDP)
  • Concurrent
  • Radio-sensitizing
  • Radiotherapy (RT)
  • Synergistic effect

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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