Leanna Stokes, a 36-year-old gymnastics manager from New Rochelle, New York, had grown accustomed to inquiring about her treatment options during visits with her oncologist. Stokes faced the daunting challenge of metastatic pancreatic cancer. Her oncologist frequently referenced “KAY-ras,” highlighting a mutation on the KRAS gene, known to make cancers more aggressive. For Stokes, this mutation represented a potential lifeline.
“She always mentioned this — KRAS, KRAS, KRAS,” Stokes recalled her oncologist saying. As she underwent numerous chemotherapy sessions, Stokes would motivate herself by thinking, “It’s there. It’s there. It’s there. Then finally, it was my turn.”
Not long ago, such optimism about KRAS might have seemed misplaced to pancreatic cancer experts. For nearly half a century after its discovery, scientists struggled to target the KRAS protein effectively. Kevan Shokat, a biochemist at the University of California, San Francisco, eventually discovered a way to treat a rare subset of KRAS mutant cancers, but the initial drugs offered limited success. Only about 1% of pancreatic cancer patients benefited from these drugs, which showed minimal improvements and quickly led to resistance.
“We did not have a home run on the first effort,” commented Channing Der, a pancreatic cancer researcher at the University of North Carolina, Chapel Hill. “It’s fair to say we’ve been disappointed by the durability of the responses.”
Nonetheless, Shokat’s breakthrough spurred numerous companies to pursue KRAS-targeted drugs, with several new agents entering clinical trials. Revolution Medicines has emerged as a leader in this field, developing the drug daraxonrasib, which targets KRAS and associated proteins.
Stokes participated in a clinical trial for this drug, which she said transformed her life by extending her survival beyond typical expectations for her condition. The drug has also sparked significant excitement among oncologists and pharmaceutical developers. It signals a promising new direction in pancreatic cancer treatment and could lead to innovations for other KRAS-mutant cancers, including those of the lung, colorectal, and endometrial types. Besides Revolution Medicines, many other companies are actively testing potential KRAS inhibitors in clinical settings.
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