CINCINNATI — When Timothy Rice was diagnosed with pancreatic cancer in 2018, he did what many newly diagnosed patients do: He went online looking for answers.
What he found terrified him.
“I didn't know anybody that had pancreatic cancer, and it said the survival rate was like 6%,” Rice said. “And I told my wife, I said, ‘That's got to be a mistake.’ But it wasn't.”
Rice made a decision.
“I told her, 'I have to be part of that 6% because I have to be here to help take care of you,'” Rice said.
WATCH: UC researchers helped tackle an ‘undruggable’ target in pancreatic cancer
Eight years later, Rice is still here. And now, patients facing certain forms of advanced pancreatic cancer have another treatment option — one developed with help from researchers at the University of Cincinnati Cancer Center.
The U.S. Food and Drug Administration last week approved Rasonque, also known as daraxonrasib, for certain adults with metastatic pancreatic adenocarcinoma.
The once-daily pill targets RAS, including KRAS, a gene mutation that researchers have spent decades trying to target in pancreatic cancer effectively.
In a randomized clinical trial involving 500 adults with previously treated metastatic pancreatic adenocarcinoma, the patients' average survival time nearly doubled.
For a cancer in which progress has historically been difficult to come by, researchers at UC describe those extra months as a major step forward.
“That's the most remarkable thing,” said Dr. Davendra Sohal, division director of hematology and oncology at UC Health. “This drug, this pill, compared with chemotherapy, which is intravenous infusions of harsh chemotherapy medicines, makes people live twice as long, and that is unheard of in pancreas cancer.”
Sohal was one of the investigators involved in clinical trials of the drug. UC Cancer Center has treated several trial patients during the past two to three years, he said.
An ‘undruggable’ target
The FDA approval represents the latest chapter in a scientific pursuit stretching back decades.
KRAS is mutated in more than 90% of pancreatic cancers, according to Andrew Waters, an assistant professor at UC who has spent much of his career studying it.
Scientists knew KRAS was important. Figuring out how to attack it was another matter.
Waters describes the mutation like a broken light switch. Normally, KRAS can toggle between an “on” and “off” state. When mutated, Waters said, it is as though someone flipped the switch on and then sawed it off.
The result can be uncontrolled cell division and eventually invasive cancer. KRAS also helps cancer cells survive after spreading to other organs, Waters said.
That made finding a way to turn the switch off particularly important — and particularly difficult.
Sohal said researchers have pursued KRAS for more than three decades. Similar drugs showed some early success in lung cancer, but pancreatic cancer remained a challenge.
“This was a novel approach in this drug to find a way to attack this switch and turn it off,” Sohal said. “And after years of trying, this approach worked, and it has succeeded.”
From a Cincinnati lab to patients' hands
UC's connection to the drug stretches beyond its clinical trials.
Waters began collaborating with Revolution Medicines, the company that developed daraxonrasib, while completing postdoctoral work in North Carolina. He brought that collaboration with him when he started his UC laboratory in 2022.
Waters said researchers at UC helped develop and describe the preclinical compound that ultimately led to daraxonrasib.
“University of Cincinnati Cancer Center has been involved in the whole arc, from preclinical drug discovery all the way to treating patients to figuring out how to make this new class of inhibitors work even better,” Waters said.
Inside Waters' UC lab, that work continues.
An automated drug dispenser can deliver tiny amounts of different drugs to cancer cells, allowing researchers to test combinations of KRAS inhibitors and other medications. Researchers also grow pancreatic cancer cells and examine molecular markers to determine whether drugs are working as intended.
In another part of the lab, researchers receive tissue removed during surgery and attempt to grow three-dimensional clusters of cells known as organoids. Those patient-derived models can then be exposed to different drug combinations to determine how they respond.
The FDA approval made the years behind that work suddenly tangible for Waters.
“I was pretty emotional, actually,” he said. “This is what I've worked on for almost 20 years, and people have worked on it for 20 years longer than that and are still in the field.”
“To have had this unanswerable question now that we have FDA-targeted drugs for, it's huge,” Waters added. “It offers hope for patients when, previously, pancreatic cancer was essentially a death sentence for a lot of people.”
For patients, progress means hope
Rice knows the new drug is not a cure.
He also knows firsthand how difficult existing pancreatic cancer treatments can be.
He remembers his first chemotherapy treatment in September 2018. By that Sunday, he said, his entire body was in pain.
After months of chemotherapy and radiation, Rice underwent a Whipple procedure in February 2019. Complications followed. He struggled to eat and ultimately lost about 65 pounds.
“It was just a rough time after, you know, even after the surgery,” Rice said.
His cancer had not metastasized, and Rice was not part of the trials that led to Rasonque's approval.
But he has seen some of the science behind it firsthand.
Rice previously met Waters and toured the UC lab. At the time, he did not know where that research would ultimately lead.
Now he does.
“The newer drug that's out now, that it just gives people hope,” Rice said. “And people that have pancreatic cancer or are diagnosed with it need hope.”
That distinction is important.
The new drug does not erase a pancreatic cancer diagnosis. It does not mean every patient will qualify for it or experience the same results as those seen in the clinical trial.
But it gives some patients another option where options have historically been limited.
And researchers believe this approval could be the beginning of something larger.
Waters said researchers are already trying to determine how to make responses to this class of drugs last longer. Work involving RAS mutations also extends beyond pancreatic cancer into lung and colon cancers.
At UC, Sohal said clinical trials are continuing to study the drug in combination with chemotherapy and in earlier stages of cancer.
“I think the key to know is that this is the beginning, not the end,” Sohal said. “We have finally found a way to tackle this problem, but there is a lot more work to be done.”
For Rice, progress can be measured more simply.
Years after he went online and wondered how long he had left, his message to someone receiving that same diagnosis today is one he has learned through experience.
“Stay positive, don't give up and stay hopeful,” Rice said. “Your story is still being written.”
This story was reported on-air by a journalist and has been converted to this platform with the assistance of AI. Our editorial team verifies all reporting on all platforms for fairness and accuracy.
