Pancreatic cancer: Researchers discover a protein that protects the tumor and inhibits the body's defenses.

Pancreatic cancer is the third most deadly type of cancer worldwide and is resistant to most current treatments (Illustrative Image Infobae). Pancreatic cancer is one of the most difficult cancers to treat. Its danger lies in the fact that the tumor creates an environment that actively suppresses the body's defenses and prevents it from attacking. Currently, available treatments only work in a minority of patients. However, research conducted by scientists from Spain and Argentina revealed that blocking a specific protein, called PARP2, within tumor cells could change this situation. This is because inhibiting PARP2 disrupts the tumor's DNA, which could activate the body's defenses to attack it. The research, published in the journal Science Advances, was led by Neus Martínez-Bosch and José Yélamos from the Institute of Research at the Hospital del Mar in Barcelona. Researchers discovered that blocking PARP2 could improve the treatment of pancreatic cancer in the future. The study was conducted on mice (Freepik). The Argentinian scientist Gabriel Rabinovich, a researcher at the Institute of Biology and Experimental Medicine (IBYME) of the Conicet, the Faculty of Exact and Natural Sciences of the University of Buenos Aires, and the CaixaResearch Institute in Barcelona, also collaborated. Scientists from the Institute of Biomedical Research in Barcelona, the Pompeu Fabra University, and other institutions in Spain participated. Pancreatic cancer ranks third among the causes of cancer-related deaths worldwide. Its cellular environment is so hostile to the body's defenses that it makes it resistant to almost all available treatments. Drugs known as PARP inhibitors, which are proteins that repair damaged DNA, represented a breakthrough in certain cancers. However, in the case of pancreatic cancer, they only work in a group of patients: those with mutations in the BRCA1 or BRCA2 genes. Furthermore, the available PARP inhibitors do not distinguish between two similar proteins: PARP1 and PARP2. Researchers genetically eliminated the PARP2 protein in mice with pancreatic cancer and measured the effect on survival and immune response (Freepik). Previous studies had already shown that eliminating PARP1 in mice with pancreatic cancer did not change either the tumor progression or the survival of the animals. In this context, the researchers wanted to understand what role PARP2 plays in pancreatic cancer specifically. To understand what PARP2 does in pancreatic cancer, the researchers used mice with this type of tumor. They used two types: some with the Myc oncogene activated and others with the KrasG12D oncogene, the most frequent mutation in human pancreatic cancer. An oncogene is a gene that, when uncontrolled, pushes healthy cells to become cancerous. In both groups, the researchers genetically eliminated the PARP2 protein and observed what happened. The result was striking: mice without PARP2 lived 43% longer, and 75% survived for more than six months, compared to 14% of the unmodified group. A study in mice demonstrated that inhibiting the PARP2 protein allows the immune system to attack the pancreatic tumor, increasing survival by 43%. (Illustrative Image Infobae) Without PARP2, tumor cells accumulated errors in their DNA and had damaged chromosomes. Chromosomes are the structures that store DNA within the cell; when they are damaged, the cancer cell becomes much more vulnerable. This genetic disorder triggered an internal alarm called STING. This pathway produces chemical signals that alert the immune system that there are damaged cells that need to be attacked. The body's response was immediate: the number of cytotoxic T lymphocytes and NK cells, the "soldiers" of the immune system that destroy tumor cells, increased. At the same time, the presence of cells that normally protect the tumor, such as M2 macrophages and regulatory T cells, decreased. The study was only conducted on animal models and has not yet been tested in humans (Illustrative Image Infobae). The researchers concluded that selectively inhibiting PARP2 could be a real therapeutic strategy because it weakens the tumor from within and activates the body's defenses at the same time. This makes it potentially valuable for patients who do not respond to immunotherapy, a treatment that aims to have the body itself slow down the tumor. The researchers clarified that the development of specific PARP2 inhibitors is still in a very early stage, and that no drugs of this type are being evaluated in humans at this time. The results come from animal models, so more research is needed before we can talk about a real treatment for patients.