Describe for the first time the antitumor activity of RAS inhibitors in preclinical models of cholangiocarcinoma

Researchers from Cima University of Navarra, in collaboration with Revolution Medicines, have published a study that evaluates, for the first time, the antitumor activities of RAS(ON) multi-selective inhibitors in cholangiocarcinoma, a type of bile duct c

Irati Macaya, Shruti Narayanan, Elisabet Guruceaga, Celia Prior, Andrea Domingo, Aitana Ortiz, Iker Feliú, Silvestre Vicent, Konstantina Morali, Mariano Ponz, Carlos Vásquez, Paula García, Xabier Bujanda, Gabriela Novoa, Julio José Jiménez e Inés López,m

The authors also identified therapeutic combinations with the potential to improve outcomes in cholangiocarcinoma

The reactivation of the RAS oncogenic signal is fundamental in this process, similar to what has been described in lung and pancreatic cancer for the same inhibitors.”

— Dr. Silve Vicent

PAMPLONA, SPAIN, April 24, 2026 /EINPresswire.com/ -- Researchers from Cima University of Navarra, in collaboration with Revolution Medicines, have published a study that evaluates, for the first time, the antitumor activities of RAS(ON) multi-selective inhibitors in cholangiocarcinoma, a type of bile duct cancer with a poor prognosis and high unmet medical need.

Using preclinical models of cholangiocarcinoma, “Our group observed that pharmacological blockade of the KRAS oncogene using RAS(ON) multi-selective inhibitors has a very pronounced antitumor effect, indicating that KRAS mutant cholangiocarcinoma depends on aberrant signaling of the RAS pathway”, explains Dr. Silve Vicent, principal investigator of the Oncogenes and Effector Targets Group at Cima, who led the study.

Revolution Medicines had previously reported the antitumor activity of the investigational agent daraxonrasib, a RAS(ON) multi-selective inhibitor in a panel of preclinical models, including non-small cell lung, pancreatic and colorectal cancer. “The preclinical results of this study, as well as the responses to daraxonrasib observed in two cholangiocarcinoma patients from our Phase 1/2 clinical trial in patients with previously treated advanced solid tumors, provide evidence to support further clinical evaluation of RAS(ON) inhibitors, such as daraxonrasib, in patients with cholangiocarcinoma”, highlights Dr. Jingjing Jiang, vice president of Translational Research at Revolution Medicines and co-senior author of the study.

The study further delves into the mechanisms of resistance to RAS(ON) multi-selective inhibitors in models of cholangiocarcinoma, revealing that "the reactivation of the RAS oncogenic signal is fundamental in this process, similar to what has been described in lung and pancreatic cancer for the same inhibitors", details Dr. Silve Vicent.

With the aim of obtaining deeper and longer lasting responses, the researchers combined the inhibitors with the current standard of care treatment in cholangiocarcinoma, which is based on chemotherapy plus immunotherapy. "We observed that the antitumor activity was much greater in the context of the combination, notably increasing median time to tumor doubling in multiple preclinical models of cholangiocarcinoma", emphasize Drs. Rodrigo Entrialgo and Konstantina Morali, first authors of the study.

The study, conducted at the Cancer Center of the University Clinic of Navarra, and which also involved researchers from IDIBAPS, Hospital Clínic, VHIO, Biogipuzkoa, and CIC affiliated with CIBERONC and CIBEREHD, was published in the scientific journal Cancer Cell.

The work was funded by Revolution Medicines, as well as by public funds from the Ministry of Science, Innovation and Universities, and by private donations such as the José Baringo León grant.

Maria Pilar Huarte Tirapu
Cima Universidad de Navarra
+34 948 19 47 00
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