For decades, pancreatic cancer has been one of the most difficult cancers to treat. The deadly cancer happens when infectious cells grow out of control in the tissues of the pancreas. Now, a new class of drugs targeting a long-elusive genetic mutation may offer real hope.
“The most exciting thing that’s going on right now, is that some of the most common genetic mutations we know of in pancreatic cancer, are finally having drugs that seem to work against them,” says Robert McWilliams, MD, a medical oncologist and the Deputy Director of OSF HealthCare Cancer Institute. “They’re in clinical trials right now, but we may see drug approvals as early as this year for these new therapies called KRAS inhibitors. Almost all pancreatic cancer tumors have those mutations. If these drugs are as promising and work as well as we hope, it should make a tremendous difference for pancreatic cancer.”
Why this moment matters in pancreatic cancer treatment
Historically, treatment options for pancreatic cancer have advanced slowly compared to other cancers.
“Pancreatic cancer treatment hasn’t evolved as quickly as I’d like. We’ve had more complex chemotherapy regimens that work incrementally better,” Dr. McWilliams says. “Trying to put those together into a plan for patients using more neoadjuvant therapies (giving chemotherapy to shrink a tumor before surgery) is something we’ve done a lot more of in the last few years.”
Even with incremental improvements, outcomes have remained challenging – largely because of how pancreatic cancer behaves.
The challenge of a “silent” disease
Pancreatic cancer, one of the deadliest forms of gastrointestinal cancer, is often diagnosed late, when treatment options are more limited. According to 2015-2021 data from the National Cancer Institute, only 13.3% of people survived five or more years after being diagnosed with pancreatic cancer. Nearly 68,000 people were diagnosed with pancreatic cancer in 2025, almost 52,000 of them died from the disease.
“One of the things that’s most challenging about pancreatic cancer, is that it can be there without causing specific symptoms. Even though a lot of people with advanced pancreatic cancer do have symptoms commonly, it is a very difficult cancer to detect early,” Dr. McWilliams says. “Because of that, oftentimes people present with advanced or metastatic disease.”
Therapeutic cancer vaccines are also in development right now. Promising results from post-operative mRNA-based vaccines have suggested an immune response is possible, and patients may have better outcomes. More trials are in progress to evaluate this further.
Targeting KRAS: A long-standing goal
According to the Lustgarten Foundation, the largest private funder of pancreatic cancer research in the world, KRAS mutations are central to the disease.
KRAS is a gene that helps control when cells grow and divide. Normally, it works like a switch, turning growth on when the body needs it, and off when it doesn’t. But when KRAS mutates, that switch can get stuck in the “on” position, causing cells to grow nonstop and eventually form cancer.
While KRAS mutations are found in about 11% of all cancers, pancreatic cancer depends on it more than almost any other. In fact, more than 90% of pancreatic ductal adenocarcinomas – the most common type of pancreatic cancer – have a KRAS mutation. That’s why researchers see KRAS as one of the most important and promising targets in the fight against pancreatic cancer.
One of the biggest challenges right now is creating drugs that can shut down the KRAS mutations most seen in pancreatic cancer, especially KRAS-G12D, which shows up in nearly half of all cases. Another key goal is developing treatments that can target several KRAS mutations at the same time. The good news: researchers are actively working on it, with more than 60 RAS-focused drugs currently in development.
New drugs moving through late-stage trials
According to Revolution Medicines, Inc., a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, the U.S. Food and Drug Administration (FDA) has granted a non-transferrable voucher for its drug daraxonrasib (RMC-6236) under the FDA’s Commissioner’s National Priority Voucher pilot program.
Daraxonrasib is being studied in two global Phase 3 clinical trials: RASolute 302 in patients with previously treated metastatic pancreatic ductal adenocarcinoma and RASolve 301 in patients with previously treated metastatic non-small cell lung cancer.
Symptoms that should not be ignored
Even with promising advances, early detection remains critical.
“One of the things is called painless jaundice. If you turn yellow (jaundice), and you’re not having abdominal pain, that is a classical sign for pancreatic cancer,” Dr. McWilliams points out. “The most common symptom people notice is weight loss. Most of us are trying to lose weight at any moment in time, but sometimes it’s a little too easy and the weight starts dripping off. When that happens, that’s something to say ‘hey, that’s great!’ But maybe I should get that checked out.”
Reducing cancer risk and improving outcomes
Dr. McWilliams says lifestyle choices can play an important role in reducing cancer risk and improving outcomes after diagnosis:
- Don’t smoke cigarettes
- Don’t vape
- Avoid drinking alcohol
- Maintain a healthy lifestyle, including a healthy weight and regular physical activity
Those diagnosed with cancer tend to do better when they engage in more physical exercise. Regular activity can also help protect against other health concerns, including heart disease, neurological disorders and chronic illness.
***Courtesy of OSF HealthCare***
