They find the Achilles heel of this deadly tumor in 9 out of 10 people.

immunotherapy This represents new hope in the fight against cancer, but not all tumors respond to this treatment. He pancreas cancerfatal to 9 out of 10 diagnosed people, does not respond to currently approved medications, but this terrible fact could change thanks to a new discovery that showed how to deal with it.

Immunofluorescence of pancreatic tumor; PGLYRP1 protein is highlighted in green. / Bruno Sainz (IIBM-CSIC-UAM).

Biomedical research specialists have obtained interesting results in their search for new targets that attack resistant cells such as cancer stem cells which are mainly responsible for tumor initiation, metastasis formation and treatment resistance.

How can you attack the cells that cause pancreatic cancer?

A recent study carried out by the Supreme Scientific Research Council (CSIC), dependent on the Ministry of Science, Innovation and Universities (MICIU), and published in the journal GUT describes it You can fight pancreatic cancer stem cells with the antibacterial protein PGLYRP1.which acts as tumor protection.

When eliminated, the defense is able to recognize tumor cells and kill them. This will allow the development of new immunotherapies that target the root of pancreatic cancer and improve treatment in the future.

The study was led by three researchers: Bruno SainzHead of the Cancer Stem Cells and Fibroinflammatory Microenvironment Group at the Sols Morreale Institute of Biomedical Research (IIBM), CSIC-UAM and the Biomarkers and Personalized Approach to Cancer (BIOPAC) Group at the Ramón y Cajal Institute for Medical Research (IRYCIS).); Christopher Heeschenfrom the Candiolo Cancer Institute (IRCCS), Italy, and Susana Garcia Silvascientist at the National Center for Cancer Research (CNIO).

How is the Achilles heel of pancreatic cancer discovered?

Over the past ten years, three scientists have led a joint project in which Iidentified a population of pancreatic cancer stem cells (CSCs) present in mouse models of the disease.. These cells, known as the tumor root, are responsible for relapses after treatment with chemotherapy or radiation therapy. Surprisingly, pancreatic cancer is also one of the tumors most resistant to immunotherapy. However, to date, the mechanisms by which CSCs manage to avoid their elimination by the immune system are unknown.

As a result of this collaboration, peptidoglycan recognition protein 1, PGLYRP1, was identified as one of the causes of immune evasion in CSCs using animal models and patient samples. This work describes for the first time the role of this protein in pancreatic cancer, which is produced in excess in stem cells. This discovery lays the foundation for the development of treatments for this disease.

Possible therapy against the root of pancreatic cancer

“When we eliminate PGLYRP1 from tumor cells, we observe that the immune system responds by attacking these cells, which prevents the formation of a primary tumor and the spread of tumor cells to form metastases,” explains Bruno Sainz, group leader at IIBM. “We are now developing treatments that will block or eliminate this protein, in the hope of combining them with current treatments and attacking stem cells in a different way,” he adds.

Over the past four years, Juan Carlos Lopez Gil, the first signatory of this work, deciphered why CSCs produce this protein in pancreatic cancer: “We observed that immune system cells try to destroy tumor cells by producing tumor necrosis factor, but PGLYRP1 is very similar to this factor and interacts with the same receptor, blocking it,” he points out. For the researcher, this means that “ROCs protect themselves by using a partial key (PGLYRP1) to block the lock (receptor) and thus avoid death due to tumor necrosis factor (full key).”

What surprises the researchers is that a protein used by our defenses to fight bacteria is used by pancreatic cancer to protect against the same defenses. “A future priority will be to understand the mechanisms by which tumor cells abuse physiological processes to retrain the environment surrounding the tumor to respond to it,” says co-author García-Silva.

The study was funded by the La Caixa Foundation, the Fero Foundation, the Pancreatic Cancer Association, the Spanish Association of Pancreatology, the Spanish Association Against Cancer, the Carlos III Institute and the Ministry of Science, Innovation and Universities, among other organizations. as part of the CIBERONC program for the treatment of gastrointestinal tumors.

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