Aurora Kinases as Potential Therapeutic Targets for Tumors with pRB and/or MYCN Dysregulation

Dysregulation of signaling pathways facilitated by the RB1 tumor suppressor gene or the MYC family of oncogenes is often observed in various malignancies. Identifying drug targets for such cancers is challenging, as RB1 mutations are typically loss-of-function alterations, while MYCN is difficult to target pharmacologically due to its intrinsically disordered structure. Recent studies, including our own investigations in retinoblastoma, have emphasized the potential of targeting aurora kinases (AURKs), specifically aurora kinase A (AURKA) and aurora kinase B (AURKB), as favourable therapeutic strategies for cancers driven by dysregulation of pRB and/or MYCN. In this review, we discuss the rationale for targeting AURKs as a treatment strategy and their functional roles. In addition, we review the status of AURKA-specific inhibitors in clinical evaluation and their associated adverse effects. Finally, we cite the emerging therapeutic strategy of proteolysis targeting chimeras (PROTACs) as an innovative means to selectively degrade AURKs, offering a novel approach to targeted cancer therapy.