Figure 1.

Targeting mitosis for cancer treatment. (a,b) Representation of G2 interphase and the stages of mitosis. A description of the main cellular changes at each stage is presented. The progression throughout mitosis is monitored by the spindle assembly checkpoint activity (SAC ON and SAC OFF). (c) Activity of mitotic proteins during G2 and mitotic phases. MPS1, Aurora B, and PLK1 kinases are involved in several processes, being activated from G2 of interphase to telophase/cytokinesis. Aurora A and Eg-5 proteins ensure proper bipolar spindle shape, remaining activated from G2 to metaphase. CENP-E is required for accurate kinetochore–microtubule attachments, operating from prometaphase to metaphase. (d) SAC modulation by targeting mitotic proteins. MPS1 and Aurora B inhibition leads to SAC override, followed by massive chromosome missegregation and cell death. PLK1, Aurora A and Eg-5 inhibition induces spindle defects, while CENP-E inhibition promotes chromosome misalignment, leading to SAC activation, which in turn arrests cells in mitosis. Under mitotic arrest, the cell undergoes death or alternative pathways, namely G1 arrest/senescence, or continues cycling. (e) Second-generation antimitotics in clinical trials. Summary of antimitotic drug targets in different phases of clinical trials and current status. Created in BioRender.