title: Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme (Review).
abstract: Cell metabolism can be reprogrammed by tissue hypoxia leading to cell transformation and glioblastoma multiforme (GBM) progression. In response to hypoxia, GBM cells are able to express a transcription factor called hypoxia inducible factor-1 (HIF-1). HIF-1 belongs to a family of heterodimeric proteins that includes HIF-1α and HIF-1β subunits. HIF-1α has been reported to play a pivotal role in GBM development and progression. In the present review, we discuss the role of HIF-1α in glucose uptake, cancer proliferation, cell mobility and chemoresistance in GBM. Evidence from previous studies indicates that HIF-1α regulates angiogenesis, metabolic and transcriptional signaling pathways. Examples of such are the EGFR, PI3K/Akt and MAPK/ERK pathways. It affects cell migration and invasion by regulating glucose metabolism and growth in GBM cells. The present review focuses on the strategies through which to target HIF-1α and the related downstream genes highlighting their regulatory roles in angiogenesis, apoptosis, migration and glucose metabolism for the development of future GBM therapeutics. Combined treatment with inhibitors of HIF-1α and glycolysis may enhance antitumor effects in clinical settings.
authors.affiliation: Department of Hospital Pharmacy, Shanghai Eighth People's Hospital, Jiangsu University, Shanghai 200235, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Hospital Pharmacy, Shanghai Eighth People's Hospital, Jiangsu University, Shanghai 200235, P.R. China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Hospital Pharmacy, Shanghai Eighth People's Hospital, Jiangsu University, Shanghai 200235, P.R. China.
authors.forename: Xing-Li
authors.initials: XL
authors.lastname: Fu
authors.affiliation: Department of Hospital Pharmacy, Shanghai Eighth People's Hospital, Jiangsu University, Shanghai 200235, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guang
authors.affiliation: Department of Health Technology and Informatics, Hong Kong Polytechnic University, Hung Hom, Kowloon Hong Kong, SAR, P.R. China.
authors.forename: Shing-Shun Tony
authors.initials: ST
authors.lastname: To
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D058990:Molecular Targeted Therapy
chemical_list: D000970:Antineoplastic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit