Category: RevMed

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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