Dual Targeting of PI3K and HDAC by CUDC-907 Inhibits Pediatric Neuroblastoma Growth
The dysregulation of PI3K, HDACs, and MYCN are very well noted for promoting multiple cancer types, including neuroblastoma (NB). Individuals upstream regulators of MYCN, including HDACs and PI3K, was proven to suppress cancer growth. In our study, we evaluate different NB patient datasets to show that top PI3K and HDAC expression is correlated with overall poor NB patient survival. High PI3K level can also be discovered to be connected rich in MYCN level and NB stage progression. We repurpose a dual inhibitor CUDC-907 like a single agent to directly target both PI3K and HDAC in NB. We use within vitro methodologies to look for the effectiveness and selectivity of CUDC-907 using six NB and three control fibroblast cell lines. Our results reveal that CUDC-907 considerably inhibits NB proliferation and colony growth, induces apoptosis, blocks cell cycle progression, inhibits MYCN, and enhances H3K9Ac levels by inhibiting the PI3K/AKT signaling path and HDAC function. In addition, CUDC-907 considerably inhibits NB tumor development in a 3D spheroid tumor model that recapitulates the in vivo tumor growth. Overall, our findings highlight the dual inhibition of PI3K and HDAC by CUDC-907 is an efficient therapeutic technique for Fimepinostat NB along with other MYC-dependent cancers.