title: Targeting mitotic exit for cancer treatment.
abstract: Several chemotherapeutic drugs interfere with assembly of the mitotic spindle of cancer cells, leading to mitotic arrest, mediated by the spindle assembly checkpoint (SAC). However, cancer cells may be SAC-deficient and survive such treatment, due to mitotic slippage. Sensing of defective spindle assembly by the SAC, causes inhibition of the anaphase-promoting complex or cyclosome (APC/C), and blocks mitotic exit, by stabilizing APC/C substrates, such as cyclin B. Mitotic slippage may occur due to residual APC/C activity and slow cyclin B degradation. Recent preclinical data suggests that targeting mitotic exit by blocking APC/C activity is a much more efficient therapeutic approach than disturbing mitotic spindle assembly.
authors.forename: Ralph
authors.initials: R
authors.lastname: Wäsch
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008938:Mitosis / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents