{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:48:45Z","timestamp":1791319725766,"version":"4.3.1"},"reference-count":108,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glioblastoma (GBM) is characterized by its unique molecular features, such as self-renewal and tumorigenicity of glioma stem cells that promote resistance, largely resulting in treatment failure. Among the molecular alterations significant to GBM biology and treatment, mutations in isocitrate dehydrogenase (IDH) have assumed particular relevance. IDH-mutant and IDH-wild-type tumors exhibit significantly different metabolic characteristics, clinical behavior, and therapeutic sensitivities, making IDH status a critical determinant in determining prognosis and treatment strategies for GBM. In the context of cancer, chaperones were shown to promote tumor progression by supporting malignant cells over healthy ones. While heat shock proteins (HSPs) have long been implicated in the molecular mechanisms of tumor phenotype progression, recent attention has turned to CCT (chaperonin containing TCP1), orchestrating proteostasis. The chaperonin CCT is being explored as a diagnostic and therapeutic target in many cancers, including GBM, owing to its involvement in key oncogenic signaling pathways such as Wnt, VEGF, EGFR, and PI3K\/AKT\/mTOR. However, its role in the GBM-tricarboxylic acid (TCA) cycle cascade is still not well understood. Therefore, the present review highlights the potential role of the CCT complex in regulating hypoxia-inducible factor (HIF) activation by modulating enzymes responsive to metabolites derived from glucose metabolism and the TCA cycle in a manner dependent on oxygen availability and IDH mutation status.<\/jats:p>","DOI":"10.3390\/ijms27010373","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T15:30:32Z","timestamp":1767195032000},"page":"373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The TRiC\/CCT Complex at the Crossroads of Metabolism and Hypoxia in GBM: Implications for IDH-Dependent Therapeutic Targeting"],"prefix":"10.3390","volume":"27","author":[{"given":"Giusi","family":"Alberti","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2131-563X","authenticated-orcid":false,"given":"Giuseppa","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4176-8900","authenticated-orcid":false,"given":"Maria Antonella","family":"Augello","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9288-1148","authenticated-orcid":false,"given":"Francesco","family":"Cappello","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5281-1516","authenticated-orcid":false,"given":"Marta Anna","family":"Szychlinska","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine in Medical, Surgical, and Critical Care Areas (Me.Pre.C.C.), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8260-8471","authenticated-orcid":false,"given":"Celeste","family":"Caruso Bavisotto","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9948-9712","authenticated-orcid":false,"given":"Federica","family":"Scalia","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1200\/JOP.2017.025536","article-title":"Treatment of Glioblastoma","volume":"13","author":"Nam","year":"2017","journal-title":"J. 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