Pancreatic cancer | CSIC has found a way to treat one of the deadliest types of cancer in Spain

A study carried out by the Supreme Scientific Research Council (CSIC) has discovered a treatment for one of the deadliest types of cancer in Spain and the world. The work, published in the journal GUT, describes how pancreatic cancer stem cells use the antibacterial protein PGLYRP1 to evade the immune system and protect themselves from premature destruction. When the protein is removed, the defenses are able to recognize tumor cells and destroy them. This will allow the development of new methods of immunotherapy which act against the root of pancreatic cancer and will lead to improved treatment in the future.

Deadly cancer

Pancreatic cancer, which is fatal to 9 out of every 10 people diagnosed and affects more than 9,000 people in Spain and nearly half a million worldwide each year, does not respond to currently approved drugs, according to the Spanish Society of Medical Oncology.

For this reason, CSIC believes that it is necessary, based on biomedical research, to 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.

Pancreatic cancer has become an important health problem because, although it does not have a high incidence in the population, it has a high mortality rate, as explained by Dr. Teresa Macarulla in an article published by the Spanish Medical Society. At the time of diagnosis, less than 20% of patients will undergo resection given the advanced stage of the disease, and survival after surgical resection is usually 10–20 months.

Full Study

Currently, immunotherapy represents a new hope in the fight against cancer, but not all tumors respond to this treatment, CSIC emphasizes.

In recent years, we have seen an increase in the incidence of this tumor, with the majority of patients diagnosed with pancreatic cancer being between 65 and 70 years of age, although there are exceptions. Steve Jobs, Apple founder, Forges and Aretha Franklin, for example, died of pancreatic cancer.

The full study can be read in the GUT journal.

The study was led by three researchers: Bruno Sainz, head of the Cancer Stem Cells and Fibroinflammatory Microenvironment Group at the Sols-Morreale Institute of Biomedical Research (IIBM), CSIC-UAM and Biomarkers and Personalized Approaches to Cancer (BIOPAC). group) of the Ramon y Cajal Institute for Medical Research (IRYCIS); Christopher Heeschen from the Candiolo Cancer Institute (IRCCS) in Italy and Susana García Silva, a scientist from the National Center for Cancer Research (CNIO).

Resistant to immunotherapy

Over the past ten years, the three scientists have led a collaborative project in which they have identified a population of pancreatic cancer stem cells (PCS) 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.

“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 hopes of combining them with current treatments and attacking stem cells in a different way,” he added.

Over the past four years, Juan Carlos Lopez Gil, the first signatory of this work, has deciphered why CSCs produce this protein in pancreatic cancer: “We observed that immune system cells try to destroy tumor cells, causing tumor necrosis. , 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 defense mechanisms to fight bacteria is used by pancreatic cancer to protect against the same defense mechanisms. “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 Garcia-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.