In experiments with mice and in tests with tumor cell lines, the drug has the potential to combat metastasis. Researchers from USP plan clinical trial with patients undergoing chemotherapy.
A drug used to treat pulmonary hypertension significantly reduced the ability of tumor cells to migrate and invade other tissues in tests performed 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 metastasis in the liver and lungs by 47%, as well as increased survival compared to untreated animals. The study was published in the journal Scientific Reports .
“The drug ambrisentan is an inhibitor of the endothelin A receptor, which plays a role in constricting 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 has an effect on tumor cells, preventing the migration of these cells 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 at the University of São Paulo ( ICB-USP) and coordinator of the study, financed by FAPESP.
Marques conducted the work during his post-doctorate at the University of Freiburg, in Germany, in collaboration with researchers from that country and the United Arab Emirates. Currently, he coordinates 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 that it is involved in the growth and metastasis of several tumors.
“It seems that the drug’s effect is not only on the migration of tumor cells, but also on neoangiogenesis, that is, on the formation of new blood vessels necessary to feed the tumor. We are conducting experiments to prove this. If confirmed, the drug would have a systemic effect, not only inhibiting the migration of the tumor to other tissues, but also blocking the generation of new vessels that make it grow ”, says the researcher.
The benefit of the drug for the treatment of cancer has not yet been proven. Use without medical advice can pose a health risk, especially for pregnant women.
Using a technique to measure cell migration, the researchers noted that the drug significantly reduced this phenomenon in both tumor cells that received a stimulus and spontaneous migration. Strains of ovarian, leukemia, pancreas and breast tumors were tested.
Then, mice in the early stage of an aggressive breast cancer strain (4Q1) were treated for two weeks before the tumor was implanted and two weeks later. In this experiment, the reduction in metastasis was 43%, increasing the animals’ survival.
“As the metastasis of 4T1 cells occurs very quickly in mice, we started the treatment earlier, so that we could get closer to what would happen to humans”, he explains.
Now, with other researchers from the ICB-USP, Marques is preparing to carry out clinical tests. The idea is to test the drug in a group of patients who are already undergoing chemotherapy and see if they recover better than another group (control) that undergoes only standard treatment.
Although the drug has the advantage of being able to be administered orally, the researcher believes in the possibility of making a direct application in the tumor, in order to increase its effect. It has not yet been defined in what type of cancer clinical tests will be done.
O artigo Ambrisentan, an endothelin receptor type A-selective antagonist, inhibits cancer cell migration, invasion, and metastasis pode ser lido em: www.nature.com/articles/s41598-020-72960-1
By André Julião | FAPESP Agency