Abstract:
Aurora Kinase B (AURKB) and Mitotic Arrest Deficient 2 Like 2 (MAD2L2) are emerging anticancer
therapeutic targets. AURKB and MAD2L2 are the least well studied members of their protein families,
compared to AURKA and MAD2L1. Both AURKB and MAD2L2 play a critical role in mitosis, cell cycle
checkpoint, DNA damage response (DDR) and normal physiological processes. However, the oncogenic
roles of AURKB and MAD2L2 in tumorigenesis and genomic instability have also been reported. DDR acts
as an arbitrator for cell fate by either repairing the damage or directing the cell to self-destruction. While
there is strong evidence of interphase DDR, evidence of mitotic DDR is just emerging and remains largely
unelucidated. To date, inhibitors of the DDR components show effective anti-cancer roles. Contrarily,
long-term resistance towards drugs that target only one DDR target is becoming a challenge. Targeting
interactions between protein-protein or protein-DNA holds prominent therapeutic potential. Both
AURKB and MAD2L2 play critical roles in the success of mitosis and their emerging roles in mitotic DDR
cannot be ignored. Small molecule inhibitors for AURKB are in clinical trials. A few lead compounds
towards MAD2L2 inhibition have been discovered. Targeting mitotic DDR components and their
interaction is emerging as a potent next generation anti-cancer therapeutic target. This can be done by
developing small molecule inhibitors for AURKB and MAD2L2, thereby targeting DDR components as
anti-cancer therapeutic targets and/or targeting mitotic DDR. This review focuses on AURKB and MAD2L2
prospective synergy to deregulate the p53 DDR pathway and promote favourable conditions for
uncontrolled cell proliferation.
