Groundbreaking Pancreatic Cancer Drug Shows Potential for Lung Cancer Treatment

Just one week after the breakthrough cancer treatment daraxone lasib was approved in the United States for advanced pancreatic cancer, the targeted therapy is showing promise against lung cancer, the world’s leading cause of cancer-related deaths.

In a small clinical trial, tumors shrank in more than 30% of participants with non-small-cell lung cancer, the most common type of lung cancer. All participants had tumor-promoting mutations in a member of the RAS protein family and had already received other cancer treatments.

“We think these results are very promising,” says Kathryn Arbor, a thoracic oncologist at Memorial Sloan Kettering Cancer Center in New York City and author of the study, published on 2 September in the New England Medical Journal¹. “These are exciting times.”

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A large randomized clinical trial is now evaluating daraxone lasib in people with non-small-cell lung cancer. Participants will receive either the targeted drug or standard chemotherapy. Regulatory agencies, including the U.S. Food and Drug Administration (FDA), will likely require results from this trial before approving daraxone lasib as a lung-cancer treatment.

The larger study should help researchers determine how long the drug’s benefits last and how quickly tumors develop resistance. In the initial trial, some tumors began growing again after responding to treatment. “We’re now learning more about the mechanisms of resistance,” Arbor says.

Targeting RAS mutations in cancer

RAS proteins are mutated in some of the most aggressive cancers, including many pancreatic, lung and colorectal tumors. For decades, these proteins were considered “undruggable” because researchers struggled to develop compounds that could bind to and inhibit them.

Over the past decade, however, scientists have developed new strategies for targeting RAS proteins. Daraxone lasib, developed by Revolution Medicine in Redwood City, California, works as a “molecular glue.” It first binds to a common cellular protein called cyclophilin A. The resulting molecular complex creates a surface that can attach to both normal and mutant RAS molecules, blocking their interactions with proteins that promote cancer growth.

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Earlier studies showed that this approach could be effective against pancreatic cancers with RAS mutations.² In a study of 500 people with advanced pancreatic cancer, daraxone lasib nearly doubled median survival, increasing it to 13.2 months compared with 6.7 months for standard chemotherapy. Based on these findings, the FDA approved the drug on 26 August, more than six months earlier than anticipated.

“Of course, everyone is wondering what comes next,” says Channing Darr, a cancer researcher at the University of North Carolina at Chapel Hill. “Could this approach work against other cancers?”