RevMed’s pancreatic cancer drug first

The US Food and Drug Administration (FDA) in August approved Revolution Medicines’ drug for the most common form of pancreatic cancer. The RAS inhibitor Rasonque (daraxonrasib) is a first-in-class drug targeting metastatic pancreatic adenocarcinoma. Shortly after, in September, an early-stage trial showed that the drug also has promise in lung cancer. These results bolster hopes that RAS inhibitors such as Rasonque could help combat a variety of hard-to-treat cancers such as pancreatic, lung and colorectal tumors.

Rasonque blocks multiple forms of the RAS protein — mutated KRAS and other RAS proteins present in over 90% of pancreatic tumors. Unlike traditional KRAS G12C- inhibitors like Lumakras (sotorasib) and Krazati (adagrasib), which bind the ‘off’ state of the protein, Rasonque binds the RAS GTPase in its GTP-bound ‘on’ conformation that drives oncogenic signaling. The drug works through a molecular glue mechanism, binding to both the abundant cellular protein cyclophilin A and RAS, preventing RAS from interacting with its signaling partners.

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