title: Hypoxia-inducible factor in thyroid carcinoma.
abstract: Intratumoural hypoxia (low oxygen tension) is associated with aggressive disease and poor prognosis. Hypoxia-inducible factor-1 is a transcription factor activated by hypoxia that regulates the expression of genes that promote tumour cell survival, progression, metastasis, and resistance to chemo/radiotherapy. In addition to hypoxia, HIF-1 can be activated by growth factor-signalling pathways such as the mitogen-activated protein kinases- (MAPK-) and phosphatidylinositol-3-OH kinases- (PI3K-) signalling cascades. Mutations in these pathways are common in thyroid carcinoma and lead to enhanced HIF-1 expression and activity. Here, we summarise current data that highlights the potential role of both hypoxia and MAPK/PI3K-induced HIF-1 signalling in thyroid carcinoma progression, metastatic characteristics, and the potential role of HIF-1 in thyroid carcinoma response to radiotherapy. Direct or indirect targeting of HIF-1 using an MAPK or PI3K inhibitor in combination with radiotherapy may be a new potential therapeutic target to improve the therapeutic response of thyroid carcinoma to radiotherapy and reduce metastatic burden.
authors.affiliation: Hypoxia and Therapeutics Group, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Burrows
authors.forename: Muhammad
authors.initials: M
authors.lastname: Babur
authors.forename: Julia
authors.initials: J
authors.lastname: Resch
authors.forename: Kaye J
authors.initials: KJ
authors.lastname: Williams
authors.forename: Georg
authors.initials: G
authors.lastname: Brabant