by Christopher Lieu,The Conversation

KRAS (blue) has been difficult for drugs to target. Credit:Fvasconcellos/Wikimedia Commons

For a long time, the likelihood of surviving pancreatic cancer has been extremely low. For patients who were diagnosed with metastatic pancreatic cancer between 2015 and 2021, about97% died within five yearsof their diagnosis.

Pancreatic cancer is so deadly in part because there are no effective screening tests, and itrarely causes noticeable symptomsin its earliest stages. By the time a patient experiences signs, such as jaundice—a yellowing of the skin—or abdominal pain, the cancer has often already spread to other organs.

As agastrointestinal oncologist and researcherspecializing in early-phase clinical trials, I have seen the critical need for more effective therapies for patients with pancreatic cancer. For decades, successfully targeting the central mechanism that causes the vast majority of pancreatic cancers was considered impossible.

However, that narrative is rapidly changing with anew drug that can shut downthe key protein that drives pancreatic cancer, nearly doubling survival rates for patients with advanced stages of the disease.

'Undruggable' tumors

The standard treatment for advanced pancreatic cancer has historicallyrelied on chemotherapy, potent drugs designed to kill rapidly dividing cells. While chemotherapy can slow the progression of the disease, its effectiveness is often limited by the ability of pancreatic cancer cells todevelop resistance against these drugs.

Pancreatic cancer's success lies in its genetics. More than 90% ofpancreatic tumorsare driven bymutations in a gene called KRAS. This gene codes for proteins that function as switches that turn cell growth on and off. When the KRAS gene is mutated, the switch becomes permanently stuck in the "on" position, commanding cancer cells to multiply endlessly.

For decades, scientists "considered KRAS to be undruggable." The surface of the protein is exceptionally smooth, lacking the molecular pockets that standard drugs require to bind to and turn the switch off.

Because existing drugs haven't been able to target this protein, treatment for pancreatic cancer has primarilyrelied on toxic drugsthat act more like blunt instruments than precise tools. Chemotherapy attempts to control the disease through widespread cell destruction, causing significant collateral damage to healthy tissues that lead to side effects.

What is daraxonrasib?

Anew drug called daraxonrasiboffers a critical advance in treating metastatic pancreatic cancer.

Daraxonrasib is taken daily by mouth. Instead of binding toKRASdirectly, itattaches to a molecule called cyclophilin Ain cells that helps fold proteins into their final 3D structures. This protein complex is then able to bind to the active KRAS protein and shut down its ability to signal cancer cells to multiply.

The company developing the drug, Revolution Medicines, presented results on May 31, 2026, from itsPhase 3 clinical trialof 500 patients with metastatic pancreatic cancer who had received prior treatment. Compared tostandard chemotherapy, daraxonrasibnearly doubled overall survivalfrom 6.7 months to 13.2 months after diagnosis. Overall, daraxonrasib reduced the risk of death for metastatic pancreatic cancer patients by 60%.

The most common side effect is aprominent skin rash, which affected more than 86% of patients in the study. Patients also frequently dealt withstomatitis—painful swelling and sores inside the mouth—as well as diarrhea, nausea, and vomiting. However, patients taking daraxonrasib were far less likely to stop treatment due to severe side effects compared to chemotherapy, and they had improved quality of life with reduced pain.

Next steps for daraxonrasib

By successfully targeting the specific genetic mutation that drives the vast majority of pancreatic cancers, researchers have demonstrated that this "undruggable" disease is treatable with targeted therapy.

The immediate next step is regulatory review of the drug's readiness for the clinic. With data now officially published, Revolution Medicines will use these findings to seek formal approval from the Food and Drug Administration and other global regulatory bodies.

Becauseadvanced pancreatic canceris notoriously difficult to treat, breakthrough therapies that demonstrate this kind of significant survival benefit are often grantedexpedited or priority review. When daroxonrasib becomes available to patients will depend on the review timeline. Should the drug obtain approval, it could be available in clinics within months.

For the broader landscape of drug development, this milestone represents a likely shift in pancreatic cancer treatment. I expect more clinical trials exploring combination therapies pairing KRAS inhibitors with other drugs to prevent tumors from developing resistance to treatment.

Should daraxonrasib succeed, it could help set the stage for more precise, personalized, and effective treatments for pancreatic cancer in the years to come.

This article is republished fromThe Conversationunder a Creative Commons license. Read theoriginal article.

Key medical concepts Carcinoma, Pancreatic RAS Inhibitor A122 KRAS protein, human