Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy

By G. Semenza. TIPS - Trends in Pharmacological Sciences, 2012

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Hypoxia-inducible factors (HIFs) mediate adaptive physiological responses to hypoxia. In human cancers that are accessible for O2 electrode measurements, intratumoral hypoxia is common and is associated with increased risk of mortality. HIF activity in regions of intratumoral hypoxia mediates angiogenesis, epithelial-mesenchymal transition, stem cell maintenance, invasion, metastasis, and resistance to radiation therapy and chemotherapy. A growing number of drugs have been identified that inhibit HIF activity by a variety of molecular mechanisms. Because many of these drugs are already FDA-approved for other indications, clinical trials can (and should) be initiated to test the hypothesis that incorporation of HIF inhibitors into current standard-of-care therapy will increase the survival of cancer patients.

Subfields: Cancer Research, Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/b5d619f4b04f95cfd5741900e156573ec52ef95f

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Citations in the corpus

ROS Function in Redox Signaling and Oxidative Stress (2014, background): “Subsequently, HIFa translocates to the nucleus and dimerizes with HIFb, regulating metabolic adaptation to hypoxia and the expression of pro-angiogenic genes such as vascular endothelial growth factor (VEGF) [62].”
Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer. (2016, background): “Several approaches for targeting hypoxic tumor cells have been proposed including hypoxia-activated prodrugs, gene therapy, recombinant anaerobic bacteria, specific targeting of HIFs, or targeting pathways important in hypoxic cells such as the mTOR and UPR pathways (Melillo, 2007; Wilson & Hay, 201”
The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy (2015, background): “Moreover, HIF-α contributes to cancer metastasis by altering cancer cell adhesion and motility through regulation of epithelial-to-mesenchymal transition (EMT) and E-cad, ZEB1, -2 and TCF3 expression,(58) as well as migration and invasion abilities through CXCR4,(59) CAIX,(60) LOX,(61) MMP-2, and MM”
Combination therapy in combating cancer (2017, background): “VEGF acts by inducing angiogenesis in hypoxic conditions [119] and will be discussed in depth in the next section (Figure 2).”
Transcriptional Regulation by Hypoxia Inducible Factors (2013, background): “…important for maintaining oxygen homeostasis, however, are HIF targets involved in autophagy, apoptosis, redox homeostasis, inflammation and immunity, stemness and self-renewal, and metastasis and invasion (Figure 2; (Chi et al., 2006; Mole et al., 2009; Semenza, 2012b; Wenger et al., 2005).”