title: HIF-1 signaling in drug resistance to chemotherapy.
abstract: Activation of hypoxia-inducible factor 1 (HIF-1) signaling is observed in a broad range of human cancers due to tumor hypoxia and epigenetic mechanisms. HIF-1 activation leads to the transcription of a plethora of target genes that promote physiological changes associated with therapeutic resistance, including the inhibition of apoptosis and senescence and the activation of drug efflux and cellular metabolism. As a result, targeting HIF-1 represents an attractive strategy to enhance the efficacy of current therapies as well as reduce resistance to chemotherapy in tumors. Approaches to inhibit HIF-1 signaling have primarily focused on reducing HIF-1α protein levels, by inducing its degradation or inhibiting its transcription, inhibiting HIF-1-mediated transcription, or disrupting the formation of the HIF-1 transcription factor complex. To date, multiple preclinical and clinical agents have been identified that effectively inhibit HIF-1 activity through various mechanisms, likely accounting for a portion of their anti-tumor efficacy. This review aims to provide an overview of our current understanding of the role of HIF-1 in therapeutic resistance and discuss the ongoing effort to develop HIF-1 inhibitors as an anti-cancer strategy.
authors.forename: N A
authors.initials: NA
authors.lastname: Warfel
authors.affiliation: 500 University Drive, Room T4423, Hershey, PA 17033, USA. wafik.eldeiry@gmail.com.
authors.forename: W S
authors.initials: WS
authors.lastname: El-Deiry
mesh_terms: D017209:Apoptosis; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D051793:Hypoxia-Inducible Factor 1