Proteasome Inhibitors against Glioblastoma-Overview of Molecular Mechanisms of Cytotoxicity, Progress in Clinical Trials, and Perspective for Use in Personalized Medicine.

ABSTRACT: Proteasome inhibitors are moieties targeting the proteolytic activity of a proteasome, with demonstrated efficacy in certain hematological malignancies and candidate drugs in other types of cancer, including glioblastoma (GBM). They disturb the levels of proteasome-regulated proteins and lead to the cell cycle inhibition and apoptosis of GBM cells. The accumulation of cell cycle inhibitors p21 and p27, and decreased levels of prosurvival molecules NFKB, survivin, and MGMT, underlie proteasome inhibitors' cytotoxicity when used alone or in combination with the anti-GBM cytostatic drug temozolomide (TMZ). The evidence gathered in preclinical studies substantiated the design of clinical trials that employed the two most promising proteasome inhibitors, bortezomib and marizomib. The drug safet

SUBMITTER: Gozdz A 

PROVIDER: S-EPMC10670062 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature