Pancreatic cancer is one of the most difficult cancers to treat. One reason is that, in most cases, cancer cells have something like a stuck accelerator. That accelerator is called RAS.
In a normal cell, RAS works like a switch: it turns on when a growth signal needs to be transmitted, and then switches off again.
In pancreatic cancer, however, this mechanism often breaks down. In more than 90% of cases, alterations in the RAS pathway are present, frequently involving the KRAS gene, which can keep the growth signal continuously active.
It is like having the accelerator pedal stuck down: the cell keeps receiving the same message.
Grow. Divide. Keep moving forward.
A known target, but almost impossible to hit
At this point, the question seems obvious: if we know what the accelerator is, why not simply block it?
Researchers have been trying to do exactly that for decades.
The problem is that RAS is a particularly difficult protein to target with a drug. We can think of it as an almost completely smooth surface: we know it is there, but it is hard to find a “grip” that a drug molecule can latch onto.
For this reason, RAS has long been considered one of the most difficult targets in oncology.
In recent years, however, something has changed, and this is where daraxonrasib comes in.
How does it work?
Daraxonrasib belongs to a new generation of drugs designed to target RAS in its active form, the form that is sending growth signals to the cell.
Let’s go back to the car metaphor: if RAS is the accelerator that has been left pressed down, daraxonrasib aims to interfere with the mechanism that keeps it active.
What makes the drug particularly interesting is that it does not target just one specific mutation, but can interfere with several forms of RAS.
A strong biological idea, however, is not enough. It has to be shown to work in patients.
The decisive test
That is what happened in the phase III RASolute 302 trial, presented at ASCO 2026.
The study included 500 patients with previously treated metastatic pancreatic cancer.
One group received daraxonrasib, taken orally. The other received standard chemotherapy.
The goal was simple: to find out whether the new drug could help patients live longer.
The results attracted considerable attention.
Median overall survival was 13.2 months with daraxonrasib, compared with 6.7 months with chemotherapy. Almost twice as long.
The time before the disease started progressing again also increased: 7.2 months versus 3.6 months.
In addition, around 30% of patients treated with daraxonrasib showed a significant reduction in tumor size, compared with 11% in the chemotherapy group.
These numbers are especially important in a disease where treatment options remain limited once the first therapy stops working.
Why is this discovery important?
The point is not simply that there is a new drug. It is what this drug is able to target.
For decades, we have known that RAS is one of the main molecular drivers of pancreatic cancer, without being able to truly turn that knowledge into an effective treatment strategy for patients.
It is a bit like knowing exactly which switch is powering a machine, but being unable to reach it.
Daraxonrasib shows that this barrier may be overcome.
This does not mean that pancreatic cancer has suddenly become easy to treat. And it does not mean that the new drug is a cure.
The disease can still progress, and not every patient responds.
But being able to directly target one of the mechanisms that drives tumor growth represents an important step forward.
From ASCO to approval
The results were presented at ASCO, the American Society of Clinical Oncology, on May 31, 2026.
Less than three months later, on August 26, 2026, the U.S. Food and Drug Administration approved daraxonrasib for certain adult patients with metastatic pancreatic adenocarcinoma.
The approval applies to patients who have already received at least one previous systemic therapy or who are not candidates for multi-agent systemic treatment.
This does not mean that the treatment is automatically available in Europe or Italy: regulatory authorities follow different approval processes.
But the transition from an experimental therapy to an approved treatment in the United States happened remarkably quickly.
A new chapter?
Perhaps the most interesting part of the story is not even the jump from 6.7 to 13.2 months. It is what lies behind those numbers.
For years, RAS has been one of the major unsolved challenges in cancer research: a crucial target, but an extremely difficult one to reach.
Now we have evidence from a phase III trial that directly targeting this “accelerator” can translate into a real benefit for patients. It is not the end of the story.
But it may be the beginning of a new chapter in the treatment of pancreatic cancer.
Fonti
- O’Reilly EM, Wainberg ZA, Hendifar AE, et al. Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer. New England Journal of Medicine. 2026;395:325–337. DOI: 10.1056/NEJMoa2605555.
- American Society of Clinical Oncology. Oral targeted therapy slows pancreatic cancer growth, improves overall survival – RASolute 302. ASCO, 2026.
- U.S. Food and Drug Administration. FDA approves daraxonrasib for metastatic pancreatic adenocarcinoma.26 August 2026.
- Sivakumar S. Breaking the RAS Barrier in Pancreatic Cancer. New England Journal of Medicine. 2026;395:400–401. DOI: 10.1056/NEJMe2606948.
