Spanish Scientists Develop Pancreatic Cancer Therapy Without Significant Side Effects

Spanish scientists have made a breakthrough in the treatment of pancreatic cancer, developing an effective therapy in mice.

Spanish Scientists Develop Pancreatic Cancer Therapy Without Significant Side Effects
Enlarge
Spanish scientists have made a breakthrough in the treatment of pancreatic cancer, developing an effective therapy in mice. (Unsplash/Julia Koblitz)

Liputan6.com, Jakarta - Scientists from Spain has opened a new chapter in the fight against pancreatic cancer, one of the most aggressive and difficult-to-treat types of cancer.

Two leading teams of scientists have successfully developed a therapeutic approach that shows promising results in mouse models, even without severe side effects.

Dr. Mariano Barbacid and his team at the Spanish National Cancer Research Center (CNIO) pioneered a triple-drug combination therapy that effectively eliminated pancreatic tumors in mice.

Meanwhile, Dr. Bruno Sainz Jr. of the Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) focused on pancreatic cancer stem cells.

"These studies open a path to designing new combination therapies that can improve survival for patients with pancreatic ductal adenocarcinoma [the most common pancreatic cancer]. These results point the way for developing new clinical trials," the study authors stated.

Revolutionary Triple Drug Therapy from CNIO

Dr. Mariano Barbacid, Head of the Experimental Oncology Group at CNIO, along with colleagues Carmen Guerra, Vasiliki Liaki, and Sara Barrambana, have devised a clever strategy to fight pancreatic cancer.

Their therapy involves a combination of three selective drugs that work synergistically to attack the tumor from multiple angles. This approach aims to prevent cancer cells from adapting and developing resistance to treatment.

The three main drugs in this therapy are Daraxonrasib (RMC-6236), Afatinib, and SD36.

Daraxonrasib works by blocking the key growth signaling gene KRAS, which is mutated in more than 90% of pancreatic cancer cases.

Afatinib, as an irreversible EGFR/HER2 kinase inhibitor, disables the EGFR and HER2 pathways that cancer cells often use as escape routes.

The Tumors Disappeared Completely

Meanwhile, SD36 is a selective STAT3 PROTAC that disables STAT3, a stress response system that helps tumor cells survive treatment.

This combination of three drugs simultaneously blocks cancer's "main engine," its "escape pathway," and its "emergency backup system."

This strategy has proven highly effective in causing pancreatic tumor regression and preventing the emergence of tumor resistance.

In a mouse model designed to mimic human pancreatic cancer, the tumors disappeared completely.

More importantly, the tumors did not recur for more than 200 days after treatment was stopped.

Similar positive effects were also observed in genetically engineered mice and in tumors taken from human patients grown in the laboratory.

Unlike traditional chemotherapy, which often causes severe side effects, this triple-drug therapy demonstrated low toxicity in animals, with mice tolerating the treatment well without serious side effects.

Uncovering the Secrets of Pancreatic Cancer Stem Cells

On the other hand, Dr. Bruno Sainz Jr., a molecular oncologist at the Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM) and the Autonomous University of Madrid, focuses his research on cancer stem cells (CSCs) in pancreatic ductal adenocarcinoma (PDAC).

His research group seeks to understand how these cancer stem cells evade the immune system, which is key to developing more effective therapies.

Dr. Sainz's team discovered that pancreatic cancer stem cells produce peptidoglycan recognition protein 1 (PGLYRP1).

This protein allows cancer cells to hide from detection and destruction by the immune system. The discovery of this mechanism provides an important basis for developing new targeting strategies.

Furthermore, the researchers identified a new class of compounds that specifically target cancer stem cells.

These compounds reduce the potential for tumor formation with low secondary toxicity.

When PGLYRP1 is removed from cancer stem cells, immune cells successfully recognize and destroy these harmful cells.This research demonstrates that targeting pancreatic cancer stem cell metabolism can be highly beneficial for patients.

The new compound, patented by Dr. Sainz's team, demonstrated potent antitumor effects in mice with patient-derived tumors, including pancreatic cancer, with low toxicity.

The results of this study have been published in the leading journal Nature Communications and provide the basis for future clinical trials.