Researchers succeed in completely eliminating most common pancreatic cancer in mice: What we know about the study

Researchers at the Spanish National Cancer Research Center (CNIO) announced that in an experiment on mice, they managed to completely eliminate the most common type of pancreatic cancer in humans. This is a medical milestone led by the director of the Experimental Oncology Group, Mariano Barbacid.

The study is published in the journal PNAS (Proceedings of the National Academy of Sciences), with Carmen Guerra as co-lead author and Vasiliki Liaki and Sara Barrambana as first authors.

In this regard, the researchers explained that the results set the course for developing new clinical trials.

"These studies open an avenue for designing new combination therapies that may improve survival in patients with pancreatic ductal adenocarcinoma [the most common pancreatic cancer]," the authors stated in PNAS.

The researchers used specific inhibitors targeting one of the three fronts and observed complete and sustained tumor regression in the laboratory in mouse models that had previously been implanted with cancer cells. "The group's strategy was to target the three fronts with a single inhibitor," the authors reported in PNAS.

"The CNIO group's strategy was to block the action of the KRAS oncogene at three points, instead of just one - it is more difficult for a beam to split if it is fixed to the ceiling at three places, instead of just one point. And indeed, after genetically removing three molecules from the KRAS signaling pathway in mouse models, the tumors disappeared permanently," the study explained.

Similarly, the researchers noted that translating this strategy to patients would require identifying drugs capable of blocking the KRAS molecular pathway at the same three points. For their experiments, the team used a triple therapy combining an experimental KRAS inhibitor (daraxonrasib), a drug approved for certain lung adenocarcinomas (afatinib) and a protein degrader (SD36).

The treatment was applied to three mouse models of pancreatic ductal adenocarcinoma, and in all induced "significant and durable regression of these experimental tumors without causing significant toxicities," the authors wrote.

"This study describes a triple combination therapy ... that induces robust regression of experimental models of pancreatic ductal adenocarcinoma, and prevents the emergence of resistance. This triple combination is well tolerated in mice," they state in PNAS.