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Author Topic: Ferroptosis in Cancer Treatment: More Than One Way to Skin a Cat  (Read 454 times)

Offline danialthomas

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Ferroptosis in Cancer Treatment: More Than One Way to Skin a Cat
« on: September 12, 2021, 04:57:41 pm »
Besides apoptosis, other mechanisms of cancer-cell death include ferroptosis, necroptosis, and pyroptosis. This posting deals with ferroptosis. I will talk about necroptosis and pyroptosis in future postings.

The term ferroptosis was first coined in 2012 to describe the programmed cell death due to the iron-mediated overaccumulation of oxidatively-damaged, cytotoxic phospholipids called lipid peroxides. Due to the higher rates of proliferation and DNA synthesis in cancer cells vs. normal cells, cancer cells have greater requirements for and contain much more iron than normal cells. This distinct difference between cancer cells vs. normal cells can and should be exploited.

In an important study that was just published, scientists at the University of British Columbia believe they may be one step closer to defeating cancer after finding what they call the disease’s “Achilles’ heel.” Their study uncovered a protein that fuels cancer when tumor oxygen levels are low (tumor hypoxia). It enables cancer to adapt and survive and become more aggressive. This protein is called CAIX (Carbonic Anhydrase #9) and it helps cancer cells spread (metastasize) to other organs.

Cancer depends on the CAIX enzyme to survive. By inhibiting its activity, the scientists believe we can effectively stop cancer cells from growing and spreading. The CAIX enzyme effectively blocks cancer cells from ferroptosis-mediated cell death. According to one of the study authors, Dr. Shoukat Dedhar, “Combining inhibitors of CAIX, including SLC-0111, with compounds known to bring about ferroptosis results in catastrophic cell death and debilitates tumor growth.”

The scientists found that targeting CAIX acidifies intracellular pH, disrupts redox homeostasis, and creates vulnerability to ferroptosis. So, if you have metastatic cancer and desperately need new treatment options, do you wait a decade or more to see if experimental compound SLC-0111 becomes an FDA-approved drug? Do you wait while approved drugs that induce ferroptosis are developed? Or does your doctor put on or his or her “translational-research” hat and consider using natural compounds such as spermidine to inhibit CAIX and piperlongumine to induce ferroptosis? I have my answer, but your doctor will need to answer it for you after carefully studying the references provided below.

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

References:

Chafe S, Vizeacoumar F, Venkateswaran G, Nemirovsky O, Awrey S, et.al. Genome-wide synthetic lethal screen unveils novel CAIX-NFS1/xCT axis as a targetable vulnerability in hypoxic solid tumors. Science Advances. 27 Aug 2021: Vol. 7, No. 35, eabj0364.
Davis RA, Vullo D, Supuran CT, Poulsen SA. Natural product polyamines that inhibit human carbonic anhydrases. Biomed Res Int. 2014;2014:374079.
Yamaguchi Y, Kasukabe T, Kumakura S. Piperlongumine rapidly induces the death of human pancreatic cancer cells mainly through the induction of ferroptosis. Int J Oncol. 2018 Mar;52(3):1011-1022.

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 brand names, dosages, or treatment advice. That is for your doctor to determine after they carefully study 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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