In a family of killer diseases, pancreatic cancer has long been one of the scariest. It could grow undetected for years, and by the time most people knew something was wrong, their prognosis was grim. The vast majority of patients, nearly 90 percent, would die within the first five years of their diagnosis. Even as other cancers saw their mortality rates drop in recent years, pancreatic cancer’s death rate actually increased slightly from 1999 to 2020.
And despite their best efforts, scientists felt stuck. In the 1980s, they identified a gene, KRAS, that seemed to be pivotal to the uncontrolled cell growth that drove the disease’s development. But over and over again, most treatments in clinical trials failed. Dr. Anirban Maitra, director of NYU Langone’s Laura and Isaac Perlmutter Cancer Center and a longtime pancreatic cancer researcher, told me that pharmaceutical companies came to regard pancreatic cancer as a “graveyard” for future drug development. Experts feared the gene was, in effect, “undruggable,” Maitra said.
But recent breakthroughs have brought what once seemed impossible within reach. A group of researchers is preparing to publish results from their clinical trial, already reported in the New York Times, that found a KRAS-targeting pill called daraxonrasib roughly doubled survival, from seven months to 13 on average, among a group of patients who had metastatic pancreatic cancer and had already tried chemotherapy.
“For the first time, there is some optimism in this disease,” Maitra told me. “Oncologists who have been treating this cancer for decades have always been so pessimistic about the fact that so many trials have failed. These patients, unfortunately, live for a few months and die. But now we finally have the foundation on which to build.”
Effectively treating pancreatic cancer — or even possibly, some day, curing it — will ultimately demand more than one successful clinical trial. It’ll require improving the full spectrum of care, which means identifying who is at risk, detecting the disease early, and producing even more effective treatments that can offer patients hope of many more years to live, not just more months.
We are getting closer to being able to diagnose and treat pancreatic cancer with remarkable precision. Here’s what it will take to get all the way there — and what everyone should know.
Doctors are getting better at figuring out who’s at risk
One major problem with pancreatic cancer is that your pancreas is buried deep in your abdomen. You could have cancer growing there for years with no symptoms. Improving the outlook starts with detecting it early — and that work begins with figuring out who is most at risk.
Many people, and even doctors, may not be aware of what to look out for, Maitra told me. There have been some high-profile deaths that temporarily put the disease in the public eye — actor Patrick Swayze, tech titan Steve Jobs — but it hasn’t been the focus of major awareness campaigns like breast or even more recently colon cancer. Pancreatic cancer accounts for about 3 percent of all cancer cases — but more than 8 percent of cancer deaths, about 39,000 every year.
Smoking, age, and obesity are all considered to be risk factors — but that is something pancreatic cancer shares with many other types of cancer. One unique risk factor is the sudden onset of adult diabetes, especially when accompanied by weight loss, Maitra said.
“If you’re like a 65-year-old and you’re presenting with new-onset diabetes and you just lost 10 pounds, I would be very worried about that person. I’d make sure I get some tests done on that person,” Maitra said. “Awareness is so important.” He clarified that most new-onset diabetes in an adult is just that, and isn’t a reason to panic. Still, he said, the connection is something more people and health care providers should be aware of.
New artificial intelligence programs could also help doctors identify who is most at risk. Hospitals are starting to experiment with scanning electronic health records or genetic samples, Maitra said, and singling out patients who may be at higher risk based on their medical history or the presence of certain genes that are associated with a greater chance of developing pancreatic cancer (including the breast cancer-causing gene BRCA2).
Clinicians have better tools for detecting pancreatic cancer early
Once doctors identify people who are at risk, they can deploy a host of new surveillance tools to look for pancreatic cancer’s development.
Blood tests, commonly referred to as liquid biopsies, have received a lot of investment, as well as media attention. Some companies aspire to create a test that could search for multiple cancers from one sample, but in the meantime, single-disease versions have shown promising if not quite ironclad results — including for pancreatic cancer. One blood test developed by Oregon Health & Science University had an 85 percent accuracy rate in diagnosing early-stage pancreatic cancer when it was used in tandem with an existing antigen test.
Once again, AI programs could help doctors get ahead of the disease. A recent study found that an AI program developed by Mayo Clinic researchers and used to examine routine abdominal CT imaging scans could spot pancreatic cancer at nearly double the detection rate of two human radiologists, finding the disease up to three years before a normal clinical diagnosis would occur.
“This is where AI can really help because they can pick out subtle patterns that the human eye can miss,” Maitra said.
Scientists are developing better pancreatic cancer treatments
Once doctors find the pancreatic cancer, they can treat it — and their options are getting better there too.
Maitra said the best treatment remains surgical removal plus therapy — and the smaller the tumor, the better, which is why early detection is so essential. It also prevents the cancer from having more time to metastasize and spread.
Even after surgery, the cancer can come back. But new vaccines are showing promise in preventing that kind of recurrence; small preliminary studies have identified multiple vaccine candidates that allowed patients to live longer without a relapse and survive overall longer than the historical norms for pancreatic cancer patients.
And for the people facing the most dire scenario, when their cancer cannot be removed by surgery, that’s where the new treatments targeting KRAS — the gene that drives pancreatic cancer’s growth — could be a game-changer.
To dramatically simplify the scientific breakthrough here, KRAS has been described by researchers as a “greasy ball” that for a long time no drug molecules were able to attach themselves to. As the Times reported, Kevan Shokat, a scientist at the University of California San Francisco, figured out how to make a molecule attach to KRAS in 2013; around the same time, Greg Verdine at Harvard University was working on a molecular “glue” that could disable KRAS. The new drugs build on this research to deliver a compound to the gene that can slow the out-of-control cell growth that causes pancreatic cancer.
But we should think of daraxonrasib, which seems likely to receive FDA approval, as the “ground floor” for this class of drugs, Maitra told me. Many people still do not respond to the treatment or experience severe side effects. The drug also stops working after a period of time, as people’s bodies develop a resistance to it. But other drugs that combine different molecules in an attempt to extend the treatment’s effectiveness are already in the pipeline.
In the future, pancreatic cancer treatment could end up becoming a combination of all of the above: early detection, surgical removal to get the bulk of a tumor out, with vaccines and/or KRAS-based treatments used to prevent the cancer from coming back. And people who can’t undergo surgery for some reason might try a combination of vaccines and KRAS-targeting drugs.
The work is far from finished. But for the first time, after decades of disappointments, there is real reason for hope.
