They manage to completely eliminate pancreatic cancer tumors in mice

BarcelonaA new door has opened to treatments for one of the deadliest cancers: pancreatic cancer. Researchers at the Spanish National Cancer Research Centre (CNIO) have, for the first time, completely eliminated pancreatic tumors in experimental mouse models using a triple therapeutic combination. The study focused on pancreatic ductal adenocarcinoma, the most common type of tumor. The researchers devised a strategy that targets three key aspects of this cancer: the mutation that initiates the tumor (called KRAS) and the two proteins involved that promote the proliferation, survival, and growth of this cancer (called EGFR and STAT3). After six years of work, the curative efficacy of this triple therapy has been demonstrated. The results have been published in the scientific journal Proceedings of the National Academy of Sciences.

This is how the study worked

Specifically, the triple therapy was tested in three experimental mouse models: one with implanted tumor cells, one genetically modified, and one carrying human cancer cells. The mice implanted with tumor cells in the pancreas were treated with a combination of inhibitors. Specifically, RMC-6236, a KRAS inhibitor; afatinib, an EGFR inhibitor; and SD36, a STAT3 degrader. This resulted in the complete and lasting regression of this type of cancer. The animals survived without any obvious alterations for at least 250 days. In fact, analysis of their pancreases revealed no tumor remnants or any surrounding tissue (known as stroma). Therefore, the mice can be defined as tumor-free. Following this, the researchers tested the triple therapy in genetically modified mice, aiming to approximate the characteristics of human tumors. All the animals showed a reduction in their tumor burden, with complete regressions in nine of the twelve mice, which lived at least 100 days disease-free and without relapses. In another test, using RMC-6236 as monotherapy, they managed to double survival in all the mice, but none survived the treatment. Finally, the research group injected the tumors from six human patients into a total of 18 immunodeficient mice. Although these tumors lacked the same properties as when they were in the patients, they did retain some of their characteristics. In 16 of the 18 mice treated with the triple therapy, the tumor disappeared, with no relapses observed in 80 of the 120 days of treatment.

The research, led by Mariano Barbacid, director of the Experimental Oncology Group at the CNIO (Spanish National Cancer Research Centre), was funded by the Cris Against Cancer Foundation. The research team, which includes Carmen Guerra as co-senior author and Vasiliki Liaki and Sara Barrambana as first authors, highlighted that, in addition to achieving a "significant and lasting regression" of these tumors, the triple therapy did not cause "significant toxicities" in the animals.

When will it be available for humans?

Barbacid explained that the process of bringing the triple therapy to a human clinical trial will be lengthy because it requires funding and progress through the corresponding regulatory processes. If everything moves at an appropriate pace, the researcher is confident that these studies could be underway within three years. However, he highlighted that the KRAS inhibitor, RMC-6236, also known as daraxonrasib and developed by the biotechnology company Revolution Medicines, could be authorized later this year or in early 2027. According to studies by this company, the metastatic inhibitor allows for a 14-month survival rate, thus doubling that achieved with chemotherapy regimens. In Spain, more than 10,300 cases of pancreatic cancer are diagnosed each year, and only between 8% and 10% of patients survive five years after diagnosis.