A study conducted in 2016 by the Belgian researchers Diether Lambrechts and Bernard Thienpont, and published in the journal ‘Nature’, showed that the lack of oxygen in the tumor cells produces changes in the gene expression of the cells, which contributes to the cancer growth.
In addition, the work showed that adequate maintenance of the oxygen supply in tumors could inhibit epigenetic aberrations, which would open a new way to create new anti-cancer drugs targeting these aberrations or blood vessels.
Cancer appears by chance or carcinogenic factors that cause the DNA of a single cell to mutate and rapidly expand to other cells. These genetic mutations alter normal cell function and help the growth and survival of cancer cells.
In addition to these genetic changes, the tumor cells produce epigenetic changes that, although do not affect the genetic code, can considerably disrupt the function of the genes, to the benefit of the cancer cells.
The origin of these changes is still not known with accuracy, although Belgian researchers have investigated a frequent genetic alteration, hypermethylation, capable of silencing the expression of tumor suppressor genes and allowing their excessive growth.
“Our study shows that these epigenetic alterations are caused by the environment of the tumor and, more specifically, by the lack of oxygen. Oxygen is needed by the enzymes that normally remove methyl groups from DNA. When there is a shortage of oxygen, the excess methylation is maintained, causing hypermethylation, and even more, this lack of oxygen accounts for up to half of the hypermethylation in the tumors. Although we have dedicated a large part of our efforts to breast tumors, we have also shown that this mechanism has an equally broad impact on the bladder, colon, head and neck, kidney, lung and uterine tumors”, said Lambrechts.
The discovery of the relationship between the lack of oxygen and the growth of the tumor was the result of analyzing more than 3,000 tumors of patients and studying whether the supply of tumor oxygen is capable of slowing the progression of cancer.
A hypothesis that, in mice, the researchers proved, since they observed that when the blood supply is normalized, it is possible to stop the epigenetic alterations that are produced.
“Our results can have a huge impact on cancer management because, first of all, we could use epigenetic aberrations to control the oxygen supply of a tumor, which allows us to better predict how it will behave and make better decisions. In addition, it sheds light on existing therapies targeting blood vessels, which not only help deliver chemotherapy to cancer, but also inhibit new epigenetic aberrations”, said Thienpont.
Scientists study whether tumor DNA analysis can be used to predict tumor oxygenation. “We want to know if it is not only possible to inhibit, but to reverse some of these epigenetic aberrations,” said Dr. Lambrechts.
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