Mitotic spindle apparatus and spindle-assembly checkpoint (SAC) machinery (SAC)

The mitotic spindle apparatus is a complex macromolecular machine composed of microtubules and associated proteins that orchestrates the accurate segregation of chromosomes during cell division [1]. The spindle-assembly checkpoint (SAC), or mitotic checkpoint, is the regulatory mechanism that monitors the attachment of chromosomes to the spindle microtubules, delaying the onset of anaphase until all chromosomes are properly bi-oriented [1, 2]. In cancer, these processes are often dysregulated, leading to chromosomal instability and aneuploidy, which are hallmarks of tumor progression [2]. Therapeutic strategies targeting this machinery include microtubule-targeting agents (MTAs) like taxanes and vinca alkaloids, as well as newer inhibitors targeting mitotic kinases such as Aurora kinases and Polo-like kinases [3, 5]. These agents work by either stabilizing or destabilizing microtubules or by inhibiting the signaling enzymes required for spindle assembly and checkpoint control [3, 4]. While highly effective in treating various malignancies, these therapies often face challenges such as dose-limiting toxicities like peripheral neuropathy and the development of drug resistance [4, 5]. Understanding the molecular intricacies of the spindle and its checkpoint remains a critical area of research for developing more selective and less toxic anti-cancer therapies [2, 3].

Other names

Mitotic apparatusSpindle assembly checkpointM-phase checkpointSpindle checkpointMitotic checkpoint

Microtubule stabilization, microtubule destabilization, inhibition of mitotic kinases (e.g., Aurora kinases, Polo-like kinases), and inhibition of kinesin motor proteins (e.g., KSP/Eg5).