'Overlap cancer oxygen': for which they gave the Nobel Prize in medicine

The 2019 Nobel Prize in Physiology or Medicine was shared by two American and one British scientists. The Nobel Committee said in a statement that the prize was awarded "for the discovery of the mechanisms by which cells sense and adapt to changes in the level of available oxygen." Writes about this with the BBC.

Фото: Depositphotos

The 2019 Nobel Prize in Physiology or Medicine was shared by two American scientists - Gregg Semenza of Johns Hopkins University in Baltimore and William Kaelin Jr. of the Dana-Farber Cancer Institute in Boston - and their British colleague Sir Peter Ratcliffe of Oxford. The scientists conducted their research independently, but together they "point the way for the development of promising new ways to combat anemia, cancer and other diseases," the report said.

What is the essence of the discovery?

The level of oxygen in the body determines normal blood supply to cells, healthy metabolism and the amount of energy - it is produced by mitochondria (they are found in almost all living cells) from nutrients entering the body with food, also with the participation of oxygen.

At the same time, the amount of oxygen available to cells is not constant: it can fall or increase depending on many factors - from the intensity of breathing and the air we breathe (for example, it may be polluted or rarefied), to hormonal emissions and various types of diseases.

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The simplest example that each of us has encountered is the compression of blood vessels due to clothing that is too tight or when applying a tourniquet.

When oxygen becomes insufficient, our body has to adapt - it turns on saving and compensation mechanisms.

But to do this, cells must first “feel” that they lack oxygen, using some special mechanism - and how exactly this happens, scientists could not understand for decades.

Moreover, this issue is by no means idle, because disruption of this mechanism has the most serious consequences: prolonged oxygen starvation can ultimately lead to irreversible changes in the tissues.

Particularly sensitive to oxygen deficiency are the heart, liver, kidneys and central nervous system.

What does cancer have to do with it?

Scientists have long known that oxygen levels in the body as a whole are monitored by special receptors adjacent to the carotid artery - carotid bodies. When oxygen becomes scarce, they send signals to the brain to regulate breathing rate. Therefore, for example, we begin to breathe more often when walking fast or other physical activity.

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In addition, at the beginning of the last century, scientists found that during hypoxia, the hormone erythropoietin is released. It is produced in the kidneys and stimulates the production of red blood cells, red blood cells that carry oxygen molecules. However, what mechanism ensures this reaction has long remained a mystery.

After conducting experiments on mice, Gregg Semenets found that the lack of oxygen somehow affects the sections of DNA responsible for the production of erythropoietin.

Sir Peter Ratcliffe studied this phenomenon in parallel - and both scientists discovered that the mechanism that allows cells to sense a lack of oxygen works in almost all tissues, and not just in the kidneys, where the necessary hormone is produced.

Semenza continued his research and discovered a protein complex, which he named HIF - “hypoxia-inducible factor.” It binds to DNA and can inhibit or stimulate the production of erythropoietin.

But what determines what the reaction will be?

Oncologist William Kelin helped to answer this question, trying to solve a completely different problem. He studied a fairly rare genetic disease (Hippel-Lindau disease) that seriously increases the risk of cancer.

In the process, he discovered that this was due to a malfunction in the VHL gene. At the same time, cancer cells with a damaged gene reacted very sensitively to a lack of oxygen, but when healthy VHL was introduced there, the reaction returned to normal.

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It turned out that VHL is responsible for the breakdown of one of the components of the HIF protein complex and changes its shape depending on oxygen saturation - which leads to changes in DNA expression.

Thus, the cells “sense” the lack of oxygen and compensate for this deficiency due to the metabolic rate.

If hypoxia lasts a long time, the body responds to oxygen starvation by building new blood vessels and actively producing red blood cells. For example, climbers are preparing for high-altitude ascents.

However, exactly the same mechanism is activated during the rapid growth of new tissue - for example, an aggressive cancerous tumor. If you turn it off, this growth can be slowed down or even stopped completely. That is why the discoveries of Kelin, Ratcliffe and Semenza can find wide application in oncology.

As ForumDaily wrote earlier:

• Nobel Prize for medicine awarded for the study of hormones that produce cells with a lack of oxygen. Three people received it at once - scientists from the USA and Great Britain.

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