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Drugs for Pulmonary Hypertension May Become an Option Against Cancer Everyday

Publicado em 05 abril 2021

The study was published in the journal Scientific Reports and published by the Fapesp news agency

A drug used to treat pulmonary hypertension significantly decreased the ability of tumor cells to migrate and invade other tissues in tests on pancreatic, ovarian, breast, and leukemia tumor lines. In addition, in mice with an aggressive form of breast cancer, the drug reduced the incidence of metastases to the liver and lungs by 47% and increased survival compared to untreated animals.

“The drug ambrisentan is an inhibitor of the endothelin A receptor, which plays a role in the narrowing of blood vessels. So it is used to treat pulmonary hypertension [normalmente causada por doenças autoimunes como lúpus e esclerose sistêmica]. In the laboratory, we saw that the drug had an effect on tumor cells and prevented these cells from migrating to other tissues, in addition to other effects that we are still investigating, ”explains Otávio Cabral Marques, a researcher at the Institute of Biomedical Sciences of  University̵ of São Paulo (ICB-USP) and coordinator of the study funded by FAPESP.

Marques led the work during his postdoctoral work at the University of Freiburg in collaboration with researchers from this country and the United Arab Emirates. He is currently coordinating a project supported by FAPESP in the Young Researcher modality.

The type A endothelin receptor is known to be expressed in the endothelium, the layer that lines the inner wall of blood vessels, and in cells of the immune system. Other studies have also shown it to be involved in the growth and metastasis of multiple tumors.

“It seems that the drug works not only on tumor cell migration, but also on neoangiogenesis, which is the formation of new blood vessels that are necessary to nourish the tumor. We are doing experiments to prove this. If this were confirmed, the drug would have a systemic effect and not only inhibit the migration of the tumor into other tissues, but also block the creation of new vessels that allow it to grow, ”says the researcher.

The drug’s use in treating cancer has not yet been established. Use without medical advice can pose a health risk, especially to pregnant women.

Experiments

Using a technique to measure cell migration, the researchers found that the drug significantly reduced this phenomenon both in tumor cells that received a stimulus and in spontaneous migration. Strains of ovarian, leukemia, pancreatic and breast tumors were tested.

Then, early stage mice of an aggressive breast cancer strain (4Q1) were treated two weeks before the tumor was implanted and two weeks later. In this experiment, the reduction in metastasis was 43%, which increased the survival of the animals.

“Because 4T1 cell metastasis occurs very quickly in mice, we started treatment in advance so we could get closer to what would happen to humans,” he explains.

Marques is now preparing to conduct clinical tests with other researchers from the ICB-USP. The idea is to test the drug on a group of patients who are already undergoing chemotherapy and see if they are recovering better than another group (control) who are only receiving standard treatment.

Although the drug has the advantage of being able to be administered orally, the researcher believes in the possibility of direct application in the tumor to increase its effects. The type of clinical cancer test to be used has not yet been defined.

O artigo ambrisentan, an endothelin receptor type A selective antagonist, inhibits the migration, invasion and metastasis of cancer cells.

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