Sensitisation of Cancer Cells to MLN8237, an Aurora-A Inhibitor, by YAP/TAZ Inactivation

**Background:** The transcriptional co-activators YES-associated protein (YAP) and transcriptional coactivator with PDZ-motif (TAZ) play a crucial role in promoting the expression of cell cycle-related genes, thereby facilitating tumor cell growth. MLN8237, a potent inhibitor of aurora-A kinase, has shown limited patient response as a monotherapy. Thus, combining it with other therapies may improve its efficacy.

**Materials and Methods:** YAP and TAZ were depleted using siRNA in YAP/TAZ-dependent OVCAR-8 and MDA-MB-231 cell lines, which were then treated with MLN8237. Additionally, MLN8237 was combined with fluvastatin, a drug that limits the nuclear localization of YAP/TAZ, to explore potential combination therapy in vitro.

**Results:** Silencing YAP or TAZ made these cell lines more sensitive to MLN8237, leading to apoptosis and a reduction in aurora-A kinase levels. MLN8237 also decreased YAP/TAZ expression. The combination of MLN8237 and fluvastatin significantly reduced cell viability in OVCAR-8 and MDA-MB-231 cell lines.

**Conclusion:** Combining MLN8237 with small-molecule agents that inactivate YAP/TAZ, such as statins, may represent a novel therapeutic strategy for treating YAP/TAZ-dependent cancers.