Pancreatic cancer success story stems from 'untreatable' KRAS target

Liana Stokes had a habit of asking her oncologist about her next treatment, and with good reason. Stokes, 36, a gymnastics manager from New Rochelle, New York, had metastatic pancreatic cancer, one of the most difficult diagnoses in oncology. Her oncologist kept mentioning two syllables, “KAY-ras,” referring to the KRAS gene mutation in her cancer. Mutations in this gene can make the cancer more aggressive. But for Stokes, it was the key to potentially extending his life.

“She always said, ‘KRAS, KRAS, KRAS,'” Stokes said of her medical oncologist. As Stokes underwent chemotherapy treatment after chemotherapy, she told herself, “It’s there. It’s there. It’s there. And finally, it’s my turn.”

Just a few years ago, this might have sounded strange to pancreatic cancer experts. In the nearly 50 years since KRAS was first discovered, scientists have struggled to effectively treat the cancer protein. When Kevan Shokat, a biochemist at the University of California, San Francisco, finally discovered a way to treat a rare subset of KRAS-mutated cancers, the first generation of drugs had been clinically disappointing. Although about 1% of pancreatic cancer patients were able to receive it, the drug only marginally improved outcomes and resistance quickly developed.

“It wasn’t a home run in the first inning,” said Channing Darr, a pancreatic cancer researcher at the University of North Carolina at Chapel Hill. “To say we were disappointed with the durability of the response would be an understatement.”

But once Shokat showed it was possible, more and more companies jumped into developing drugs for KRAS, and new drugs now move into clinical trials on a regular basis. The leader in this field is Revolution Medicines, which developed the drug daraxone lasib, which targets KRAS and related proteins.

This was a drug Stokes obtained through a clinical trial. She said it changed her life and allows her to live much longer than most patients who are diagnosed. The study has also generated great excitement among oncologists and drug developers, who say it heralds a new era in pancreatic cancer medicine and could lead to new treatments for other cancer types with KRAS mutations, including lung, colorectal, and endometrial cancers. In addition to Revolution Medicines, dozens of other companies are testing promising KRAS inhibitors in the clinic.

STAT+ exclusive story