Mechanisms of cisplatin-induced apoptosis and of cisplatin sensitivity: Potential of BIN1 to act as a potent predictor of cisplatin sensitivity in gastric cancer treatment

Satoshi Tanida, Tsutomu Mizoshita, Keiji Ozeki, Hironobu Tsukamoto, Takeshi Kamiya, Hiromi Kataoka, Daitoku Sakamuro, Takashi Joh

Research output: Contribution to journalReview article

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Cisplatin is the most important and efficacious chemotherapeutic agent for the treatment of advanced gastric cancer. Cisplatin forms inter- and intrastrand crosslinked DNA adducts and its cytotoxicity is mediated by propagation of DNA damage recognition signals to downstream pathways involving ATR, p53, p73, and mitogen-activated protein kinases, ultimately resulting in apoptosis. Cisplatin resistance arises through a multifactorial mechanism involving reduced drug uptake, increased drug inactivation, increased DNA damage repair, and inhibition of transmission of DNA damage recognition signals to the apoptotic pathway. In addition, a new mechanism has recently been revealed, in which the oncoprotein c-Myc suppresses bridging integrator 1 (BIN1), thereby releasing poly(ADP-ribose)polymerase 1, which results in increased DNA repair activity and allows cancer cells to acquire cisplatin resistance. The present paper focuses on the molecular mechanisms of cisplatin-induced apoptosis and of cisplatin resistance, in particular on the involvement of BIN1 in the maintenance of cisplatin sensitivity.

Original languageEnglish (US)
Article number862879
JournalInternational Journal of Surgical Oncology
StatePublished - Sep 18 2012
Externally publishedYes


ASJC Scopus subject areas

  • Surgery
  • Oncology

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