Literature review on mitotic cell death-based cancer therapy.

Abstract

Mitotic cell death (MCD) is commonly used interchangeably with mitotic catastrophe. However, these events have inherent differences and will be defined as two separate entities here. With MCD as the focus, this review discusses the various mitosis-specific anti-cancer targets like microtubules, Aurora-A kinase, Polo-like kinase 1, kinesin spindle protein and centromere-associated protein E. The inhibitions of these targets cause different forms of mitotic spindle defects which activates the spindle assembly checkpoint. Despite the effectiveness of these inhibitors, some cancer cells still slip out of mitosis and enter the next G1 phase, where they may or may not die. To prevent this, the direct targeting of mitotic exit has been proposed and it has been shown to be successful. These different target inhibitions all lead to MCD, which is regulated by effectors like the Bcl-2 family of apoptotic proteins and caspases. Although mitotic arrest and MCD are commonly linked, the exact mechanism behind this correlation is still unclear. To facilitate the understanding of this correlation, this review suggests the use of quantum dots, a nanotechnology-based technique. Also, with the achievement of the aforementioned target inhibitors, the discovery of other mitosis-specific targets will further advance the development of more anti-cancer therapies.