An international research team has identified a gene that favors the proliferation of brain metastases. Thanks to an inhibitor molecule, the scientists prevented the metastatic spread in the central nervous system of mice.
Credit: Nature
Discovered a can therapeutic target to prevent the metastasis of various forms of cancer to spread in brain and in the rest of the central nervous systeman event associated with a significant worsening of the oncological disease and the poor prognosis. Those of the brain, in fact, are incurable. Metastases, ie cancer cells that begin to circulate in the body and affect organs other than that of primary tumorare the leading cause of cancer death. Being able to prevent its proliferation and spread would be an extremely significant achievement in the fight against cancer. Now researchers have identified a specific gene associated with brain metastases, which blocked with ad hoc drugs could prevent their proliferation, saving the lives of many patients. In tests on mice the spread of metastases in the central nervous system was blocked.
The potential therapeutic target was identified by an international research team led by Portuguese scientists from the Faculty of Medicine of the University of Lisbon, who collaborated closely with colleagues from the Department of Neurosurgery and the Neuropathology Laboratory of the Hospital of Santa Maria, of the German Cancer Consortium of the Faculty of Medicine and University Hospital of Düsseldorf (Germany) and of various other institutes. The scientists, coordinated by Professor Claudia C. Faria, professor at the “João Lobo Antunes” Institute of Molecular Medicine (IMM) of the University of Lisbon, reached their conclusions after having “hunted” for recurring molecular phenomena linked to brain metastases. Across the RNA sequencing of thirty patients with metastases to the central nervous system, the researchers identified the upregulation of a protein expressed by the homonymous gene called UBE2C, “which ensures proper transition from metaphase to anaphase, across different primary tumor origins,” as explained in the study abstract. Simply put, it favors the mitosi of cancer cells.
To confirm the role of this gene, Professor Faria and colleagues involved 89 other patients with the same clinical condition; investigations have shown that upregulation of UBE2C is associated with a worsening prognosis. Studies on mouse models (mice) have also shown that high levels of the protein expressed by the UBE2C gene catalyze the proliferation of brain metastases. Specifically, it determines “a broad leptomeningeal dissemination”. Having determined the central role of this gene, the scientists searched for hundreds of already approved drugs and other compounds capable of inhibiting the action of UBE2C. “We tested 650 drugs already approved for use by patients by the FDA (Food and Drug Administration, USA) or used in phase 3 or 4 clinical trials, and identified a small molecule inhibitor that decreases UBE2C levels and prevents the spread of tumor cells in the central nervous system, when administered at an early stage of the disease”, study co-author Eunice Paisana said in a press release. The molecule in question is called dactolisib (it’s a dual inhibitor PI3K/mTOR) and when used early in mice prevents the development of leptomeningeal metastases induced by the UBE2C gene.
The discovery could lead to a potentially revolutionary treatment capable of blocking brain metastases, but these are preliminary investigations on mice and before reaching clinical trials (human trials) a very long process is needed to determine its efficacy and safety. “Our goal during this research has always been to contribute to the discovery of new therapeutic targets. In our team, we study patient biological samples to generate knowledge that could contribute to clinical practice in the future,” Dr. Paisana specified. Professor Faria points out that brain metastases are “the leading cause of cancer-associated morbidity and mortality” and new therapies need to be found. The details of the research “UBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease” have been published in the specialized scientific journal Neuro-Oncology Advances.