The FDA’s Wednesday approval of a new pancreatic cancer drug concludes a lengthy effort to target one of oncology’s most elusive proteins.
Experts view the drug as a first step, potentially ushering in a new era of therapies for multiple cancer types.
Academic counts show at least 79 comparable agents are under investigation in 238 clinical trials worldwide.
Major pharmaceutical firms—including Eli Lilly, Pfizer, Amgen, and AstraZeneca—are racing to develop similar agents, following the lead of Revolution Medicines’ daraxonrasib, marketed as Rasonque.
Taken twice daily, the drug inhibits mutant KRAS, a protein long viewed as an attractive yet elusive target that drives most pancreatic cancers and many lung, colon, and other tumors. For years, KRAS’s smooth surface appeared undruggable, lacking a clear binding site for therapeutic intervention.
Recent scientific breakthroughs have overturned that view, demonstrating KRAS’s vulnerability. Since roughly 2024, research intensity in this area has surged.
“This is not just pancreatic cancer,” said Dr. David S. Hong, an oncologist at MD Anderson Cancer Center in Houston and one of the leaders of an early safety study of daraxonrasib. He compared its landmark approval to the advent about 15 years ago of a powerful class of immunotherapy drugs, called immune checkpoint inhibitors, that are now used against a broad array of tumors.
Cancer often evades single‑agent therapy, raising hopes that combining modalities could suppress tumors more effectively. Studies are already evaluating KRAS‑targeting agents alongside other treatments in multipronged regimens, and daraxonrasib’s approval may spur additional combination trials.
Experts consensus holds that this nascent drug class will require combination strategies to improve efficacy and durability, noted Channing Der, a KRAS pioneer who directs labs in North Carolina and Berlin monitoring experimental agents and trials.
Revolution Medicines, a San Francisco‑based firm with no prior approved products, is regarded as the field’s leader. Its flagship trial evaluates daraxonrasib as an initial therapy after pancreatic cancer diagnosis—rather than as a second‑line option after chemotherapy, the population for which the drug received approval.
The company is also advancing a related agent, zoldonrasib, which shows early activity in lung cancer. Revolution has partnered with Bristol Myers Squibb, Tango Therapeutics, and Summit Therapeutics to explore combination regimens using its KRAS inhibitors.
Daraxonrasib is not the inaugural KRAS inhibitor; Amgen and Bristol Myers Squibb each secured approval years ago for lung‑cancer agents that target KRAS. Those drugs produced limited benefit, as they acted on a single KRAS variant and only when the protein was not actively driving tumorigenesis, allowing tumors to quickly develop resistance.
Next‑generation KRAS inhibitors such as daraxonrasib aim to overcome those limitations by targeting multiple KRAS mutants and inhibiting the protein during active cancer signaling. Nevertheless, like other targeted agents, they may eventually lose efficacy as tumors recur.
KRAS belongs to a protein family mutated in roughly 20 % of human malignancies, including tumor types previously considered unresponsive to this strategy.
Breast cancer illustrates this point: KRAS mutations are uncommon in primary breast tumors, yet they can arise in metastatic disease—such as lung or liver lesions—after treatment resistance emerges.
Researchers, including Ariella Hanker of UT Southwestern’s Simmons Comprehensive Cancer Center, are considering a clinical trial to evaluate KRAS‑targeted therapy in breast cancer.
Dr. Elizabeth Jaffee, a Johns Hopkins pancreatic cancer researcher, highlighted key priorities: developing next‑generation KRAS inhibitors with reduced toxicity, overcoming resistance that drives relapse, and pairing KRAS blockers with other modalities such as immunotherapy.
“We’re all really excited, of course,” she said. But, she added, “we have a lot to do.”
Achieving these objectives will demand close cooperation among rival firms, she noted, and tensions have already surfaced publicly in one instance.
Erasca has drawn attention for early‑stage studies of its KRAS inhibitor ERAS‑0015 in lung and pancreatic cancers. The molecule closely resembles daraxonrasib; last spring Revolution Medicines’ counsel alleged patent infringement and urged Erasca to halt U.S. development. Based in San Diego and having licensed the compound from a Chinese firm, Erasca denies the claim.
