Molecular mechanisms of anti-cancer therapies

Research output: Contribution to journalReview articlepeer-review


Cell cycle checkpoints block the transition from one phase of the cell cycle to the next phase until all processes are completed. Defects in these checkpoint functions lead to genomic instability, which results in the development of malignant tumors. However, it has become known that a loss of checkpoint function is directly related to sensitivity to antineoplastic treatments. Most cancer cells are deficient in G1 checkpoint function and therefore fail to arrest in the G1 phase on exposure to genotoxic agents. Instead, they accumulate temporarily in the G2 phase. However, given that the G2 checkpoint is also partially impaired in cancer cells, they are unable to maintain G2 arrest and eventually die as they enter mitosis. This process is known as mitotic catastrophe or mitotic death. Mitotic catastrophe is an important mechanism for the induction of cell death in cancer cells by antineoplastic agents. Cells entering mitosis with DNA damage arrest at metaphase for more than 10hr without chromosome segregation and subsequently die directly from metaphase. This long-term metaphase arrest before catastrophic death is termed the "precatastrophic phase". We found that spindle check is activated during the precatastrophic phase. Therefore, inhibition of the spindle checkpoint function as a result of depletion of BubR1 or Mad2 by RNAi caused cells to escape from mitotic catastrophe and led to subsequent abnormal mitosis when DNA damage is induced. Our data suggest that a dysfunction of the mitotic checkpoint in cancer cells may confer resistance to DNA-damaging agents and malignant progression. In this review article, I would like to summarize how cancer cells are terminated by DNA-damaging agents and anti-mitotic drugs. Based on these findings, I would like to propose the novel mechanisms by which tumors become insensitive to those chemotherapeutic agents.

Original languageEnglish
Pages (from-to)688-693
Number of pages6
JournalJapanese Journal of Neurosurgery
Issue number10
Publication statusPublished - 10-2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology


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