Mitotic spindle

The mitotic spindle is a complex, dynamic macromolecular machine composed of microtubules and various associated proteins, such as kinesin and dynein motors, which is responsible for the physical segregation of chromosomes during cell division [1]. It forms during prophase and functions by attaching to chromosomal kinetochores, aligning chromosomes at the metaphase plate, and subsequently pulling sister chromatids toward opposite poles of the cell [2]. In the context of oncology, the mitotic spindle is a major therapeutic target because its disruption prevents cancer cells from completing mitosis, thereby inhibiting tumor growth [3]. Most clinically used drugs targeting this machinery, known as antimitotic agents or spindle poisons, act by binding to tubulin to alter microtubule dynamics [4]. This interference activates the spindle assembly checkpoint, leading to prolonged mitotic arrest and the induction of apoptosis [5]. However, because microtubules also play vital roles in non-dividing cells—particularly in axonal transport within neurons—these drugs are frequently associated with dose-limiting toxicities such as peripheral neuropathy [6]. Beyond tubulin-binding agents, newer therapeutic strategies aim to target specific spindle-associated motor proteins like Kinesin-5 (Eg5) or regulatory kinases like Aurora and Polo-like kinases to achieve more selective mitotic inhibition [7, 8].

Other names

Mitotic apparatusSpindle apparatusMitosis machineryMicrotubule-based mitotic machinery

Antimitotic drugs disrupt the mitotic spindle by binding to tubulin subunits, either stabilizing microtubules to prevent their disassembly (e.g., taxanes and epothilones) or inhibiting their polymerization (e.g., vinca alkaloids and eribulin), which results in prolonged mitotic arrest and subsequent apoptosis.