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Current insights and future perspectives of hypoxia-inducible factor-targeted therapy in cancer

  • Thekkuttuparambil A. Ajith EMAIL logo
Published/Copyright: September 27, 2018
Journal of Basic and Clinical Physiology and Pharmacology
From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 30 Issue 1

Abstract

Hypoxia-inducible factors (HIFs) are transcription factors that are expressed in the hypoxic tumor microenvironment. They are involved in the cellular adaptations by improving the metabolism of glucose and enhance the expression of vascular endothelial growth factor, platelet-derived growth factor and angiopoietin, thereby they play a pivotal role in the angiogenesis. Hypoxia can increase the expression of nuclear factor-kappa B which promotes the pro-inflammatory status. Abnormally high angiogenesis, inflammation, antiapoptosis and anaerobic glycolysis can augment the progression and metastasis of tumor. Hence, HIFs remain one of the promising antiangiogenic agents as well as a direct target for interfering with the energetic of cancer cells in order to regulate the tumor growth. Previous studies found agents like topotecan, acriflavine and benzophenone-1B etc. to block the HIF-α mediated angiogenesis. The effect is mediated through interfering any one of the processes in the activation of HIF such as nuclear translocation of HIF-1α; dimerization of HIF-1α with β in the nucleus; HIF-1α/HIF-2α mediated induction of VEGF or translation of HIF-1α mRNA. Despite the experimental studies on the inhibitory molecules of HIFs, none of them are available for the clinical use. This review article discusses the recent update on the HIF-targeted therapy in cancer.

Keywords: angiogenesis; apoptosis; clear cell renal cell carcinoma; hypoxia; hypoxia-inducible factor; normoxia; nuclear factor-kappa B
Corresponding author: Dr. Thekkuttuparambil A. Ajith, PhD, Professor Biochemistry, Department of Biochemistry, Amala Institute of Medical Sciences, Amala Nagar, Thrissur-680 555, Kerala, India, Fax: +91-487-2307969

  1. Author contributions: The author has accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2017-10-01
Accepted: 2018-07-31
Published Online: 2018-09-27
Published in Print: 2018-12-19

©2019 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Immune response and inflammatory pathway of ulcerative colitis
  4. Current insights and future perspectives of hypoxia-inducible factor-targeted therapy in cancer
  5. Behavior and Neuroprotection
  6. Effect of caffeine on alcohol consumption and alcohol-induced conditioned place preference in rodents
  7. Reproduction
  8. Pubertal anabolic androgenic steroid exposure in male rats affects levels of gonadal steroids, mating frequency, and pregnancy outcome
  9. Dynamics of inflammatory reaction and oxidative stress across maternal serum, placenta and amniotic fluid in laboratory rats and the role played by genistein aglycone
  10. Cardiovascular-Pulmonary Interactions
  11. Local inhibition of carbonic anhydrase does not decrease sweat rate
  12. The standardized extract of Nigella sativa and its major ingredient, thymoquinone, ameliorates angiotensin II-induced hypertension in rats
  13. Correlation between the blood level of irisin and the severity of acute myocardial infarction in exercise-trained rats
  14. Oxidative Stress
  15. Zataria multiflora extract and carvacrol affect cardiotoxicity induced by Adriamycin in rat
  16. Attenuation of oxidative stress and hepatic damage by white butterfly (Clerodendrum volubile) leaves in streptozotocin-induced diabetes in rats
  17. Proline supplementation mitigates the early stage of liver injury in bile duct ligated rats
  18. Pravastatin attenuates testicular damage induced by doxorubicin – a stereological and histopatological study
  19. Metabolism
  20. Re-establishing normal diet following high fat-diet-induced obesity reverses the altered salivary composition in Wistar rats
  21. Phytotherapy
  22. In vivo analgesic effect of different extracts of Hopea odorata leaves in mice and in silico molecular docking and ADME/T property analysis of some isolated compounds from this plant
  23. Hepatoprotective activity of Tamarindus indica Linn stem bark ethanolic extract against hepatic damage induced by co-administration of antitubercular drugs isoniazid and rifampicin in Sprague Dawley rats
  24. Case Report
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https://doi.org/10.1515/jbcpp-2017-0167
Keywords for this article
angiogenesis; apoptosis; clear cell renal cell carcinoma; hypoxia; hypoxia-inducible factor; normoxia; nuclear factor-kappa B

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Immune response and inflammatory pathway of ulcerative colitis
  4. Current insights and future perspectives of hypoxia-inducible factor-targeted therapy in cancer
  5. Behavior and Neuroprotection
  6. Effect of caffeine on alcohol consumption and alcohol-induced conditioned place preference in rodents
  7. Reproduction
  8. Pubertal anabolic androgenic steroid exposure in male rats affects levels of gonadal steroids, mating frequency, and pregnancy outcome
  9. Dynamics of inflammatory reaction and oxidative stress across maternal serum, placenta and amniotic fluid in laboratory rats and the role played by genistein aglycone
  10. Cardiovascular-Pulmonary Interactions
  11. Local inhibition of carbonic anhydrase does not decrease sweat rate
  12. The standardized extract of Nigella sativa and its major ingredient, thymoquinone, ameliorates angiotensin II-induced hypertension in rats
  13. Correlation between the blood level of irisin and the severity of acute myocardial infarction in exercise-trained rats
  14. Oxidative Stress
  15. Zataria multiflora extract and carvacrol affect cardiotoxicity induced by Adriamycin in rat
  16. Attenuation of oxidative stress and hepatic damage by white butterfly (Clerodendrum volubile) leaves in streptozotocin-induced diabetes in rats
  17. Proline supplementation mitigates the early stage of liver injury in bile duct ligated rats
  18. Pravastatin attenuates testicular damage induced by doxorubicin – a stereological and histopatological study
  19. Metabolism
  20. Re-establishing normal diet following high fat-diet-induced obesity reverses the altered salivary composition in Wistar rats
  21. Phytotherapy
  22. In vivo analgesic effect of different extracts of Hopea odorata leaves in mice and in silico molecular docking and ADME/T property analysis of some isolated compounds from this plant
  23. Hepatoprotective activity of Tamarindus indica Linn stem bark ethanolic extract against hepatic damage induced by co-administration of antitubercular drugs isoniazid and rifampicin in Sprague Dawley rats
  24. Case Report
  25. Drug-induced optic neuropathy in a case of extensively drug-resistant pulmonary tuberculosis
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