Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer.
By C. Wigerup, S. Påhlman, D. Bexell. Pharmacology and Therapeutics, 2016
620 citations recorded by the source corpus.
Insufficient tissue oxygenation, or hypoxia, contributes to tumor aggressiveness and has a profound impact on clinical outcomes in cancer patients. At decreased oxygen tensions, hypoxia-inducible factors (HIFs) 1 and 2 are stabilized and mediate a hypoxic response, primarily by acting as transcription factors. HIFs exert differential effects on tumor growth and affect important cancer hallmarks including cell proliferation, apoptosis, differentiation, vascularization/angiogenesis, genetic instability, tumor metabolism, tumor immune responses, and invasion and metastasis. As a consequence, HIFs mediate resistance to chemo- and radiotherapy and are associated with poor prognosis in cancer patients. Intriguingly, perivascular tumor cells can also express HIF-2α, thereby forming a "pseudohypoxic" phenotype that further contributes to tumor aggressiveness. Therefore, therapeutic targeting of HIFs in cancer has the potential to improve treatment efficacy. Different strategies to target hypoxic cancer cells and/or HIFs include hypoxia-activated prodrugs and inhibition of HIF dimerization, mRNA or protein expression, DNA binding capacity, and transcriptional activity. Here we review the functions of HIFs in the progression and treatment of malignant solid tumors. We also highlight how HIFs may be targeted to improve the management of patients with therapy-resistant and metastatic cancer.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/0fe3c78609ffd2a8d014575b935b5845b3f3d66e
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In Cancer Research
In Molecular Biology
Citations in the corpus
- Role of hypoxia in cancer therapy by regulating the tumor microenvironment (2019, background): “conditions can result in an increase in the distance between the capillaries, exceeding the capacity of oxygen to diffuse [11, 12].”