The spindle assembly checkpoint: Molecular mechanisms and kinase-targeted drug discovery

Inês Lima1, Fernanda Borges1, António Pombinho2

  • 1CIQUP-IMS - Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, R. Campo Alegre s/n, 4169-007 Porto, Portugal.

Drug Discovery Today
|April 11, 2025
PubMed

Insights

The spindle assembly checkpoint (SAC) ensures accurate chromosome segregation. In cancer, targeting SAC kinases like Aurora B and MPS1 offers new anticancer strategies by overriding this checkpoint.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • The spindle assembly checkpoint (SAC) is crucial for accurate chromosome segregation during cell division.
  • SAC inactivation in cancer cells can lead to aneuploidy and cell death.
  • Understanding SAC signaling is vital for developing targeted cancer therapies.

Purpose of the Study:

  • To provide a concise overview of the spindle assembly checkpoint (SAC) signaling pathway.
  • To review recent drug discovery strategies targeting SAC kinases for cancer treatment.
  • To highlight novel anticancer agents designed to override SAC.

Main Methods:

  • Literature review of SAC signaling mechanisms.
  • Analysis of recent advancements in kinase inhibitor drug discovery.
  • Focus on targeting Aurora B and monopolar spindle kinase (MPS1).

Main Results:

  • SAC is a critical surveillance mechanism for mitotic fidelity.
  • SAC inactivation in cancer cells can be a double-edged sword, leading to cell death.
  • Targeting SAC kinases presents a promising avenue for novel anticancer drug development.

Conclusions:

  • The SAC pathway is essential for preventing aneuploidy.
  • Targeting specific kinases within the SAC pathway, such as Aurora B and MPS1, is a key strategy for developing new cancer therapeutics.
  • Overriding SAC offers a potential approach to induce cell death in cancer cells.

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