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Author Topic: Targeting Tumor Hypoxia  (Read 277 times)

Offline danialthomas

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Targeting Tumor Hypoxia
« on: October 06, 2021, 06:12:29 pm »
As a tumor grows, it soon outstrips its blood supply, necessitating the formation of new blood vessels to continue to deliver oxygen and nutrients to the tumor. To orchestrate this, cancer cells boost the production of growth factors such as VEGF (vascular endothelial growth factor) to stimulate the formation of blood vessels in a process known as angiogenesis. Unlike the carefully formed and functional blood vessels in healthy tissue, tumor blood vessels tend to be malformed and dysfunctional. As a result, blood flow in tumors is non-uniform and erratic. Some regions of the tumor will be non-hypoxic (sufficiently oxygenated), whereas other regions will be hypoxic (oxygen-deprived).

One of the main reasons that people die prematurely of late-stage cancer is treatment failure due to treatment resistance. It turns out, tumor hypoxia plays a central role in limiting the effectiveness of anti-cancer therapy. Tumor hypoxia stimulates the formation of and stabilizes (activates) hypoxia-inducible factor 1-alpha (HIF-1α). Accumulation of stabilized HIF-1α promotes a whole cascade of events that promote the proliferation and survival of cancer cells and cancer stem cells, tumor invasion, metastasis, immunosuppression, drug resistance, ferroptosis resistance, and disease recurrence. To combat this, we have the following tools at our disposal to help reverse tumor hypoxia and its effects, and improve treatment outcomes:

• Acetazolamide
• Carbogen breathing
• Curcumin
• Hyperthermia
• Intravenous ozonated saline
• Pentoxifylline
• Sulforaphane
• Transdermal carbon dioxide

Dr. Daniel Thomas, DO, MS
Mount Dora, Florida

References:

Alonzi R, Padhani AR, Maxwell RJ, Taylor NJ, Stirling JJ, Wilson JI, d'Arcy JA, Collins DJ, Saunders MI, Hoskin PJ. Carbogen breathing increases prostate cancer oxygenation: a translational MRI study in murine xenografts and humans. Br J Cancer. 2009 Feb 24;100(4):644-8.
Bahrami A, Atkin SL, Majeed M, Sahebkar A. Effects of curcumin on hypoxia-inducible factor as a new therapeutic target. Pharmacol Res. 2018 Nov;137:159-169.
Elming PB, Sørensen BS, Oei AL, et al. Hyperthermia: The Optimal Treatment to Overcome Radiation Resistant Hypoxia. Cancers (Basel). 2019;11(1):60.
Fuhrmann DC, Mondorf A, Beifuß J, Jung M, Brüne B. Hypoxia inhibits ferritinophagy, increases mitochondrial ferritin, and protects from ferroptosis. Redox Biol. 2020 Sep;36:101670.
Golunski G, Woziwodzka A, Piosik J. Potential Use of Pentoxifylline in Cancer Therapy. Curr Pharm Biotechnol. 2018;19(3):206-216.
Jing X, Yang F, Shao C, Wei K, Xie M, Shen H, Shu Y. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer. 2019 Nov 11;18(1):157.
Kim DH, Sung B, Kang YJ, Hwang SY, Kim MJ, Yoon JH, Im E, Kim ND. Sulforaphane inhibits hypoxia-induced HIF-1α and VEGF expression and migration of human colon cancer cells. Int J Oncol. 2015 Dec;47(6):2226-32.
Kuroda K, Yamashita M, Murahata Y, et al. Use of ozonated water as a new therapeutic approach to solve current concerns around antitumor treatment. Exp Ther Med. 2018;16(3):1597-1602.
Philip B, Ito K, Moreno-Sánchez R, Ralph SJ. HIF expression and the role of hypoxic microenvironments within primary tumours as protective sites driving cancer stem cell renewal and metastatic progression. Carcinogenesis. 2013 Aug;34(8):1699-707.
Said HM, Hagemann C, Carta F, Katzer A, Polat B, Staab A, Scozzafava A, Anacker J, Vince GH, Flentje M, Supuran CT. Hypoxia induced CA9 inhibitory targeting by two different sulfonamide derivatives including acetazolamide in human glioblastoma. Bioorg Med Chem. 2013 Jul 1;21(13):3949-57.
Takeda D, Hasegawa T, Ueha T, Imai Y, Sakakibara A, Minoda M, Kawamoto T, Minamikawa T, Shibuya Y, Akisue T, Sakai Y, Kurosaka M, Komori T. Transcutaneous carbon dioxide induces mitochondrial apoptosis and suppresses metastasis of oral squamous cell carcinoma in vivo. PLoS One. 2014 Jul 2;9(7):e100530.

Disclaimer:

This information is for educational purposes only and not intended or implied to be a substitute for professional medical advice, diagnosis, treatment, and monitoring by your doctor. Therefore, I cannot answer questions regarding appropriateness in your situation nor give treatment advice. That is for your doctor to determine after he or she carefully studies the references above
Located in Mount Dora, Florida, Dr. Thomas is one of the most educated, experienced, and innovative physicians in North America. Over the past 30 years, he has helped people throughout the United States and Canada to prevent and overcome disease, improve their health, slow aging, and increase their lifespan. As an active translational researcher, Dr. Thomas has spent over 35,000 hours poring over the latest scientific discoveries and translating max. discoveries into promising theories

 


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