Research proposes innovative approach for tackling an extremely aggressive form of liver cancer according to CSIC findings
In a groundbreaking development, researchers from the Spanish National Cancer Research Centre (CSIC-University of Salamanca) and the Bellvitge Biomedical Research Institute (IDIBELL) have proposed an innovative strategy to halt the growth of a particularly challenging liver cancer – cholangiocarcinoma. The study, led by Dr. Javier Vaquero and Dr. Isabel Fabregat, was published in the journal 'Signal transduction and targeted therapy'. It focuses on two proteins called NADPH oxidase 4 (NOX4) and NADPH oxidase 1 (NOX1), which are present in cancer-associated fibroblasts, not tumor cells. By simultaneously blocking these proteins using a specific drug, the study shows that it is possible to slow cancer growth in preclinical models, without directly affecting tumor cells or other tissues. This approach allows the tumor environment to be attacked, weakening the support it needs to develop. Cholangiocarcinoma is a malignant tumor that is difficult to detect in its early stages, and the mortality associated with it is very high. Intrahepatic cholangiocarcinoma, the type of cholangiocarcinoma that this study focuses on, is different from other hepatic tumors such as hepatocellular carcinoma in its response to TGF-β inhibitors. The study demonstrates that in intrahepatic cholangiocarcinoma, transforming growth factor beta (TGF-β) acts as a brake on tumor growth. However, the study suggests that inhibiting TGF-β directly may be counterproductive in the treatment of intrahepatic cholangiocarcinoma. Although the recent approval of immunotherapy has been an advance in its treatment, most patients do not respond adequately. The new findings could enhance the efficacy of immunotherapy in future research. Results in cell cultures and animal models show a significant reduction in tumor growth and an improvement in the infiltration of beneficial immune cells. The study proposes this approach as a potential way to increase patient survival. However, it is important to note that these findings have not been tested in humans yet. The next step will be to conduct clinical trials to determine the safety and efficacy of this new therapeutic approach. In the research project by CSIC-University of Salamanca and IDIBELL, new therapeutic approaches targeting the TGF-beta pathway were tested for intrahepatic cholangiocarcinoma, identifying a novel therapeutic target that specifically blocks tumor progression with fewer side effects. This study is a significant step forward in the fight against this deadly cancer.
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