The 2019 medicine Nobel Prize winner Dr. Gregg L. Semenza found out that cancers and Anemia can be cured by targeting the oxygen-regulated hypoxia-inducible factors (HIF-1s) in the cells.
What are HIF-1s and how are they related to oxygen?
We all need Oxygen to be alive. At a cellular level, oxygen is essential to cell viability as it provides an energy source (ATP) for important cellular activities. In our body, only red blood cells that contain hemoglobin can deliver oxygen for all the other cells. During a shortage of oxygen, erythropoietin (EPO) increases the production of red blood cells. Hence, more red blood cells are available to bind and deliver oxygen from the lung to the other parts of the body. Besides, vascular endothelial growth factors (VEGFs) can stimulate the formation of blood vessels in response to the lack of oxygen. By forming more blood vessels, the body can ensure that oxygen can get to other cells in different parts of the body.
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- Hypoxia-inducible factor 1 (HIF-1) regulated by oxygen tension. Source: Journal of Zhejiang University-Science B
HIFs are the oxygen sensing knob in our bodies. Hypoxia-inducible factors (HIF-1s) are composed of two different subunits-one being an oxygen-regulated HIF alpha subunit and the other being an oxygen insensitive HIF beta subunit.
The alpha subunit of the HIFs can sense the oxygen concentration changes. When the oxygen level is low, the two HIF subunits join to assemble the dimeric HIF-1s. The HIF-1s can then bind to genes that express EPOs and VEGFs. As a result, more EPOs and VEGFs are available to deliver limited oxygen to cells in different parts of the body. Meanwhile, when the oxygen level is high, fewer HIF subunits form the dimeric HIF-1s. Thus, fewer HIF-1s can bind to EPOs and VEGFs genes, which further leads to less EPOs and VEGFs proteins being expressed.
How can the researchers target the HIF-1s to cure cancer and Anemia?
Cancer is a group of diseases with abnormal cell growth. HIF-1s can be targeted to treat cancer because by inhibiting the dimeric HIF-1s, the cancer cells will have fewer EPOs and VEGFs. Therefore, the cancer cells will have much harder time oxygen and without enough oxygen, these cancer cells can die.
“By adding a small molecule that inhibits HIF-1s, added on to the other cancer drugs that patients are receiving, will allow those other drugs to be more effective in fighting cancer,’’ said Dr. Semenza
“And as for Anemia, targeting the HIF-1s could show promising effect.”
He added: “Anemia is associated with the lower-than-normal amount of red blood cells or hemoglobin. By taking a pill of a drug that increases HIF-1s activity and turns on EPO.”
The discovery of this oxygen-sensitive knob HIF-1s is a milestone in cancer and Anemia treatments. Cancers and Anemia perhaps are not that scary.
Journal Reference :
Gregg L. Semenza. Pharmacological targeting of hypoxia-inducible factors. Annual Review of Pharmacology and Toxicology, 2019; 59: 379-403 DOI: https://doi.org/10.1146/annurev-pharmtox-010818-021637
-Pricia Ouyang
Jan 27th, 2020
