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- W2896585982 abstract "Current microtubule-targeting agents (MTAs) remain amongst the most important antimitotic drugs used against a broad range of malignancies. By perturbing spindle assembly, MTAs activate the spindle assembly checkpoint (SAC), which induces mitotic arrest and subsequent apoptosis. However, besides toxic side effects and resistance, mitotic slippage and failure in triggering apoptosis in various cancer cells are limiting factors of MTAs efficacy. Alternative strategies to target mitosis without affecting microtubules have, thus, led to the identification of small molecules, such as those that target spindle Kinesins, Aurora and Polo-like kinases. Unfortunately, these so-called second-generation of antimitotics, encompassing mitotic blockers and mitotic drivers, have failed in clinical trials. Our recent understanding regarding the mechanisms of cell death during a mitotic arrest pointed out apoptosis as the main variable, providing an opportunity to control the cell fates and influence the effectiveness of antimitotics. Here, we provide an overview on the second-generation of antimitotics, and discuss possible strategies that exploit SAC activity, mitotic slippage/exit and apoptosis induction, in order to improve the efficacy of anticancer strategies that target mitosis." @default.
- W2896585982 created "2018-10-26" @default.
- W2896585982 creator A5019215930 @default.
- W2896585982 creator A5034766571 @default.
- W2896585982 creator A5035262852 @default.
- W2896585982 creator A5041458969 @default.
- W2896585982 creator A5064480114 @default.
- W2896585982 creator A5072542274 @default.
- W2896585982 date "2019-01-01" @default.
- W2896585982 modified "2023-10-02" @default.
- W2896585982 title "Mitosis inhibitors in anticancer therapy: When blocking the exit becomes a solution" @default.
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