The UB identifies a new therapeutic target to improve anticancer drugs that inhibit a key protein for the development of tumors
Src is a protein with a fundamental role in the development of tumors. However, drugs based on inhibitors of this molecule have shown limited effectiveness. Now, researchers from the BioNMR research group, from the University of Barcelona (UB) and the International University of Catalonia (UIC), led by the professor of the Department of Inorganic and Organic Chemistry of the UB, Miquel Pons, have identified a new therapeutic target with potential to improve the efficiency of this type of drugs.
Although it is not the main driver of cancer, Src influences crucial aspects of cancer cell survival, such as metastasis, migration or resistance to chemotherapy and immunotherapy, which makes this protein an attractive target for cancer. development of new therapies. So far, the four drugs that inhibit this protein have been approved mainly to treat hematological tumors, but they do not work against solid tumors such as colorectal or breast cancer, where overexpression of Src predicts a poor prognosis of the disease.
One of the main reasons for the ineffectiveness of these drugs lies in their off-target effects, that is, they often also inhibit other proteins in normal cells, causing significant toxic effects. Furthermore, these negative consequences require limiting the pharmacological dose of these medications.
These indiscriminate effects occur because the Src family is made up of diverse proteins that share domains, which are very similar and are the targets of current drugs. On the other hand, the UB team has shown that the unique domain of Src – a sequence that is not shared with the rest of the proteins in the family – also has a direct role in its oncogenic effects. In fact, previous studies by these researchers with tumor-derived cell lines have shown a 50% reduction in the invasive capacity of cancer cells by modifying the single domain.
Therefore, the new target is presented as a potentially more selective therapeutic target against cancer cells: it would leave the rest of the proteins not related to the tumor intact and would have the potential to reduce toxicity and improve efficacy in the treatment of solid tumors.