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Future prospects for mitosis-targeted antitumor therapies

期刊

BIOCHEMICAL PHARMACOLOGY
卷 190, 期 -, 页码 -

出版社

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2021.114655

关键词

Chemotherapy; Antimitotics; Bcl-2 family; Senescence; Immunotherapy

资金

  1. Spanish Ministry of Science and Innovation [SAF2016-76338-R]
  2. Gobierno de Arag ' supported by the Spanish Ministry of Science and Innovation (grant SAF2016-76338-R) and Gobierno de Arag 'on (grant LMP98_18). [LMP98_18]

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Developing new therapies targeting cell cycle regulation and mitosis has shown potential, despite many being discontinued during clinical trials. Future efforts could focus on increasing cell death signals, targeting senescent cells, and promoting antitumor immune response to enhance the efficacy of these treatments.
Dysregulation of cell cycle progression is a hallmark of cancer cells. In recent years, efforts have been devoted to the development of new therapies that target proteins involved in cell cycle regulation and mitosis. Novel targeted antimitotic drugs include inhibitors of aurora kinase family, polo-like kinase 1, Mps1, Eg5, CENP-5 and the APC/cyclosome complex. While certain new inhibitors reached the clinical trial stage, most were discontinued due to negative results. However, these therapies should not be readily dismissed. Based on recent advances concerning their mechanisms of action, new strategies could be devised to increase their efficacy and promote further clinical trials. Here we discuss three main lines of action to empower these therapeutic approaches: increasing cell death signals during mitotic arrest, targeting senescent cells and facilitating antitumor immune response through immunogenic cell death (ICD).

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