Researchers from the ICB-USP (Institute of Biomedical Sciences of the University of São Paulo) succeeded in preventing the progression of pancreatic cancer in three cellular models of the disease. The result, published in the journal New investigational drugs, of the group Springer Naturewas obtained using compound NSC305787.
Discovery, supported by FAPESPpaves the way for the development of a new therapy against this type of cancer.
By analyzing The Cancer Genome Atlas (TCGA) database, which collects information on the genetic material of more than 20,000 patients with 33 types of cancer, the researchers identified that the majority of cancer patients pancreas that had a large amount of the ezrina protein died. two to five years after the onset of tumours.
“We got this discovery after a long data mining work. This information caught our attention to carry out tests with the compound, which is an inhibitor of ezrine, because it is one of the most deadly cancers and has few therapeutic options”, explains the research coordinator, Professor João Agostinho Machado-Netofrom the Laboratory of Cancer Biology and Antineoplastics, Department of Pharmacology, ICB-USP.
The compound has been applied to three cell models of pancreatic cancer and shown to be able to prevent protein activation. “As a result, there was a higher rate of tumor cell death, which prevented growth and migration in the trials. in vitromaking them less malignant,” he says.
The application has been made in models that simulate disease tumors. These are cell lines, approved for commercial use, which have been obtained from samples donated by patients and subjected to the immortalization process.
Despite the differences between the experimental models, the cancer cells tested showed similar results.
“With the success of these early trials, we plan to assess the effects of the compound and the expression of its target further. in vitro, but now in cells obtained directly from patients with the tumor. Thus, we will have a more assertive result in view of the diversity of the results that we have obtained,” says Machado-Neto.
At the same time, researchers are evaluating other types of cancers that could benefit from the ezrine inhibitor. The group is examining responses to the compound in cervical cancer (cervical carcinoma), colon cancer and leukaemias.
Based on these results, tests will be carried out on animal models.
According to Machado-Neto, in previous studies with animal models, the inhibitor performed well in terms of pharmacokinetics (ability to reach the site of action and stay inside the body) and proved to be non-toxic.
However, there is still no way to develop drugs from it, as the compound has not yet been tested in humans. Its use is limited to research so far.
If effective in humans as well, the strategy should be important in the early and middle stages of pancreatic cancer, as it would prevent the disease from getting worse.
According to the National Cancer Institute (Inca), the disease accounts for 4% of all cancer deaths in Brazil, which corresponds to approximately 12,000 deaths per year. Also according to the agency, about 87% of Brazilian cases lead to deaths.
One of the main factors for the high mortality rate is the lack of therapeutic alternatives, which today are essentially limited to chemotherapy.
“Chemotherapy is an aggressive treatment that is adopted when the tumors are already at an advanced stage. It has no specific target, therefore, it compromises the patient’s overall health,” Machado-Neto points out.
If the thesis pointed out by the group is confirmed in clinical studies, ezrine can also be used as a biomarker of the disease to assess the severity of the disease. “This analysis can be done using a test called immunohistochemistry, which is used in laboratories to assess the characteristics of solid tumors,” he says.
The research had the participation of doctoral students: JJean Carlos Lipreri da Silvawho worked in data mining, Keli Lima, Livia Bassani Lins de Miranda e Bruna Oliveira de Almeidawhich acted in cellular and molecular tests.
He also had the collaboration of the undergraduate student Maria Fernanda Lopes Carvalho, of the course of Biomedical Sciences of the ICB-USP, who participated in the research as a scientific initiation scholarship and also worked in the mining at the TCGA.
The study on pancreatic cancer is part of a line of research implemented at the institute four years ago. It develops work that seeks to find new therapeutic targets for cancers and thus identify possible drugs.
Among the promising works, the results stand out in vitro with NSC305787 against acute myeloid leukemia and the molecule reversin against acute lymphoblastic leukemia, a finalist project for the Octavio Frias de Oliveira Prize, organized by the Octavio Frias de Oliveira Cancer Institute (Icesp) and the Leaf Group.
The article “NSC305787, a pharmacological inhibitor of ezrine, exhibits antineoplastic activity in pancreatic cancer cells” is available at: https://pubmed.ncbi.nlm.nih.gov/35477813/.
With information from the ICB-USP Communications Office.