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Pancreatic cancer has been one of the most difficult cancers to diagnose and treat. However, important progress is being made to treat pancreatic cancer as researchers and oncologists are now able to target one of the most common drivers of the disease: a gene called KRAS.
A major milestone occurred on August 26, 2026, when the U.S. Food and Drug Administration (FDA) approved daraxonrasib (Rasonque), an oral RAS-targeted therapy, for adults with previously treated metastatic pancreatic cancer. It is the first FDA-approved RAS-targeted therapy for metastatic pancreatic cancer and the first major new treatment for metastatic pancreatic cancer this decade, helping to usher in a new era of treatment options.
To better understand why this development is so important and what it could mean for the future of pancreatic cancer treatment and care, Dr. Manish Shah, Director of Gastrointestinal Oncology and Chief of the Solid Tumor Program at Weill Cornell Medicine, explains why pancreatic cancer is one of the most difficult cancers to diagnosis and treat, as well as the rapidly changing treatment landscape.
Pancreatic cancer begins in the pancreas, an organ located deep within the upper abdomen that plays important roles in digestion and regulation of blood sugar. One of the biggest challenges with pancreatic cancer is that it can grow quietly. When symptoms do occur, they can be vague and may be associated with many other conditions. Common symptoms include abdominal or back pain, jaundice, unexplained weight loss, changes in appetite and digestive problems. Often getting to the root cause of the symptoms requires several different tests.
There is currently no routine screening test for pancreatic cancer in people at average risk, unlike those in other conditions such as mammograms for breast cancer or colonoscopies for colorectal cancer. Most patients are diagnosed after the pancreatic cancer has already spread or become inoperable.
The location of the pancreas also makes treatment trickier. Dr. Shah explains that the disease's location compounds the challenge, sitting in close proximity to critical blood vessels like the celiac axis. These vessels are the way that oxygen-rich blood is delivered to the upper digestive organs, including the stomach, esophagus, spleen, pancreas, liver, gallbladder and small intestine.
For pancreatic cancer, tumors are classified in one of four ways based on where the tumor is located and if there’s involvement of any blood vessels:
Resectable: The tumor can potentially be completely removed with surgery.
Borderline resectable: The tumor has some involvement with nearby structures or blood vessels and may require additional treatment before surgery.
Locally advanced: The cancer has not spread to distant organs but has grown around important blood vessels, making surgery more difficult or impossible.
Metastatic: The cancer has spread to other organs, such as the liver or lungs.
Only a minority of patients are diagnosed with pancreatic cancer when it can be surgically removed. For patients with resectable disease, treatment may include surgery and chemotherapy, with some centers using chemotherapy before surgery to help assess the biology of the cancer. Patients with locally advanced disease may receive chemotherapy, sometimes followed by radiation or other approaches. Metastatic pancreatic cancer is generally treated with systemic therapies that travel throughout the body.
At the center of this conversation is KRAS, a protein that is mutated in over 90% of pancreatic cancer patients. For decades, researchers knew KRAS was an important target but struggled to develop drugs that could effectively block it. The KRAS protein is like a light switch that should be able to turn on and off, but a cancer-causing KRAS mutation can essentially leave that switch stuck in the “on” position. This continually sends growth signals to the cancer cell.
“The mutation changes the protein function so that it's always delivering a downstream signal,” explains Dr. Shah. “That signal tells cancer cells to survive, grow, and spread, making KRAS a critical driver of the disease.”
KRAS is considered a “driver mutation” because it occurs very early in the development of many pancreatic tumors. This can help set the cancer-forming process in motion. Dr. Shah also highlights something distinctive about pancreatic cancer’s biology: “Unlike other cancers, mutations in pancreatic cancer that lead to metastases happen early.” These genetic changes allow microscopic pancreatic cancer cells to invade surrounding tissue and spread to other parts of the body, which is another one of the reasons pancreatic cancer is often diagnosed after it has already spread.
However, not all KRAS mutations behave identically. If you think about KRAS like a pie, different mutations represent different slices. These subtypes—including G12D, G12V, G12R, and others —appear to carry different prognostic implications, an area of active research that is reshaping how specialists think about personalizing treatment. Researchers are continuing to develop an understanding of these differences so they can continue to develop even more precise therapies tailored to the molecular characteristics of each patient’s cancer.
The importance of understanding KRAS also highlights why comprehensive genetic testing remains essential for pancreatic cancer patients, both to identify actionable mutations and to determine eligibility for inherited cancer risk counseling.
Germline genetic testing uses a blood or saliva sample to look for inherited genetic changes. These mutations can be present in cells throughout the body and may have implications for family members.
Tumor genomic testing looks at the genetic characteristics of the cancer itself. Unlike an inherited mutation, a mutation found only in a tumor generally does not get passed on to a family member. Instead, this type of testing can identify mutations that may be targets for existing therapies or clinical trials. This is important in pancreatic cancer because although more than 90% of patients have a mutation in KRAS, 10% of patients do not have such a mutation. Instead, those patients may have other alterations that could potentially be targeted.
A third type of testing is called circulating tumor DNA (ctDNA) testing. Tumors can release small fragments of their DNA into the bloodstream. In some circumstances, analyzing this DNA may provide information about the molecular characteristics of the cancer when obtaining enough tissue for tumor testing is difficult.
Together, these approaches help doctors build a more complete picture of the biology of an individual patient’s cancer. KRAS may be the dominant driver in most pancreatic cancers, but genetic and tumor testing can reveal when someone’s cancer has a different set of molecular characteristics, potentially opening the door to other treatment approaches.
KRAS is part of the RAS family, a group of proteins that help control signals involved in cell growth and survival. Daraxonrasib represents an important step forward because it’s designed to targeted RAS in its active, or “on” state. This is different from traditional chemotherapy, which generally works by attacking the cell machinery in rapidly dividing cells that are necessary for cell division, helping to stop this process and the cancer cells from replicating. Rather than broadly affecting dividing cells, a targeted therapy is designed to interfere with a specific molecular process that specifically helps certain cancer cells survive and grow.
Daraxonrasib is a pan-RAS inhibitor, designed to target multiple mutations in KRAS rather than one specific KRAS alteration. It’s also an oral medication, so patients find it much more convenient than typical intravenous (IV) therapy.
The recent FDA approval of daraxonrasib followed from the positive results of the RASolute 302 clinical trial, which compared daraxonrasib to standard chemotherapy in patients with metastatic pancreatic cancer who had already progressed on their initial treatment. The results of this trial were presented during the plenary session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and showed a substantial improvement in overall survival in those taking daraxonrasib. Median survival nearly doubled, and far more patients were alive at one year on this new drug compared to chemotherapy.
Reflecting on the outcomes of the trial, Dr. Shah offers a thoughtful interpretation of what the data might mean beyond raw survival numbers. “These results also showed an increase in patient-reported quality of life, allowing patients to spend more time with family and continue activities they enjoy,” he notes.
Like any therapy, daraxonrasib comes with its own side effect profile, most notably diarrhea and a skin rash affecting many patients, particularly in the first weeks of treatment. Dermatology support and preventive strategies have become an important part of managing patients on the drug.
The approval of daraxonrasib illustrates why clinical trials matter. The treatment is now widely available to eligible patients and was only made possible by patient participation in the clinical trials that showed the benefits of this new therapy.
The current FDA approval is for people with previously treated metastatic pancreatic cancer, so those with newly-diagnosed metastatic pancreatic cancer are still recommended to receive chemotherapy for their initial treatment. This is because there is not yet enough evidence to establish daraxonrasib as a standard first-line treatment for patients who have not previously received systemic therapy. Research is currently underway to evaluate if targeting RAS earlier in the course of care can provide even greater benefit.
By continuing to establish clinical trials in this area, researchers are discovering new ways to target RAS and ultimately treat patients.
Pancreatic cancer remains a serious and challenging disease. The FDA approval of daraxonrasib does not mean that the fight against pancreatic cancer is over, but it does represent a breakthrough that would have been difficult to imagine only a few years ago.
Multiple new clinical trials are already underway, exploring combinations of RAS-targeted therapies with chemotherapy and other novel agents. These trials are studying several strategies to attack RAS and KRAS from different angles. This growing toolbox is important because as we learn more about pancreatic cancer, there will be more opportunities to match patients with precise treatments designed for the specific characteristics of their cancer.
Overall, the pace of progress in this field has accelerated remarkably in just a few short years, offering real optimism for pancreatic cancer patients and their loved ones as they face a diagnosis that has historically carried a more dire prognosis.
To learn more about pancreatic cancer, the importance of KRAS and the research changing pancreatic cancer treatment, listen to the CancerCast podcast episode on this topic where Dr. Manish Shah, alongside guest Dr. Shubham Pant from The University of Texas MD Anderson Cancer Center, break down this topic and all the details about daraxonrasib for metastatic pancreatic cancer.
Listen to the full episode on Apple Podcasts, Spotify, YouTube, or on the Weill Cornell Medicine website.
