Pancreatic Cancer: New Triple Therapy Shows Promise in Trials

Pancreatic cancer remains a formidable challenge in global health. France currently ranks as the fourth highest country worldwide in the number of pancreatic cancer cases, with nearly 16,000 new diagnoses occurring each year, according to the Institut national du cancer. The disease carries a particularly grim prognosis, with 90% of cases diagnosed at an inoperable stage, resulting in a five-year survival rate of less than 10%.

A Potential Breakthrough: The Tritherapy Approach

Researchers at the Centro Nacional de Investigaciones Oncológicas (CNIO) in Spain, led by Mariano Barbacid, are pioneering a novel strategy to combat pancreatic cancer. Their approach focuses on simultaneously blocking the action of the KRAS oncogene – present in 90% of pancreatic cancer patients – at three distinct points. As the researchers explain, this is akin to securing a beam to a ceiling with multiple anchors, making it significantly more resistant to breaking.

The tritherapy combines three treatments: daraxonrasib, a KRAS inhibitor; afatinib, a medication already approved for certain lung adenocarcinomas; and SD36, a protein degrader. Testing on three models of mice with pancreatic adenocarcinoma demonstrated “significant and durable regression of these experimental tumors without causing significant toxicities,” as detailed in a study published in December in the journal PNAS.

Did You Know? The first medications specifically targeting pancreatic cancer were only approved in 2021, marking the first notable improvement in treatment options in over half a century.

Addressing the Challenge of Resistance

Historically, new drugs targeting pancreatic cancer, first approved in 2021, have faced a significant hurdle: the development of tumor resistance after a few months of treatment. This new triple approach, however, successfully prevented the emergence of resistance in the animal models tested, representing a potentially major advancement.

What does this mean for patients? While the results are promising, Mariano Barbacid cautions against premature optimism. He states, “It is important to understand that, although we have never obtained experimental results like these before, we are not yet in a position to conduct clinical trials with this triple therapy.”

Barbacid further explains that optimizing this tritherapy for clinical use will be a complex undertaking. Despite these current limitations, he believes the findings could pave the way for new therapeutic options to improve outcomes for patients with pancreatic ductal adenocarcinoma in the near future.

Expert Insight: The development of resistance to targeted therapies is a common obstacle in cancer treatment. This research’s success in preventing resistance in animal models suggests a potentially more durable therapeutic effect, which is a critical step toward improving long-term patient outcomes.

Frequently Asked Questions

What is the KRAS oncogene?

The KRAS oncogene is mutated in 90% of people diagnosed with pancreatic cancer. Researchers are attempting to block its action to halt the growth of cancerous tumors.

What were the results of the tritherapy in mice?

The tritherapy induced “significant and durable regression of these experimental tumors without causing significant toxicities” in three models of mice with pancreatic adenocarcinoma.

Is this treatment available to patients now?

No, according to Mariano Barbacid, clinical trials with this triple therapy are not yet possible, and further optimization is needed before it can be used in humans.

Given the complexities of pancreatic cancer treatment and the potential of this new approach, what further research would you like to see prioritized?