Exploring the role and clinical implications of proteasome inhibition in medulloblastoma

Abstract

Ubiquitin proteasome-mediated protein degradation has been implicated in posttranslational oncogenesis in medulloblastoma. Current research is evaluating the clinical implications of proteasome inhibition as a therapeutic target. In medulloblastoma cell lines, proteasome inhibitors induce apoptosis and inhibit cell proliferation via multiple pathways involving activation of caspase pathways, NFκB (nuclear factor kappalightchain-enhancer of activated B cells) pathway inhibition, reduced AKT/mTOR pathway activity, and proapoptotic protein expression. Second-generation proteasome inhibitors demonstrate blood-brain barrier penetration while maintaining antitumor effect. This review summarizes the ubiquitin-proteasome system in the pathogenesis of medulloblastoma and the potential clinical implications.

Pathological implications of metabolic reprogramming and its therapeutic potential in medulloblastoma

“…In line with this, it has been demonstrated that bortezomib, a proteasome inhibitor, which was previously found to selectively kill MB cells, induces cell death in a ROS-dependent manner ( Ohshima-Hosoyama et al, 2011 ). Bortezomib treatment results in the stabilization of NOXA, a member of the Bcl-2 family, triggering apoptosis in response to high ROS levels in a p53-independent manner ( Ohshima-Hosoyama et al, 2011 ; Hoerig et al, 2021 ). A recent molecular work from Li et al, has studied the effects of Liposomal Honokiol (Lip-HNK), a small bisphenol lignin delivered into liposomes, as a potential treatment against MB ( Li et al, 2022 ).…”