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RAS-ing the bar in the treatment of KRAS-mutant cholangiocarcinoma
Minh Truong Do1, Ferdinandos Skoulidis1
1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Abstract:
Despite progress in elucidating the molecular landscape and actionable vulnerabilities of cholangiocarcinoma, clinical outcomes for patients with advanced disease remain dismal. In this issue of Cancer Cell, Entrialgo-Cadierno et al. raise the bar for the ∼20%-25% of patients with oncogenic KRAS mutations by unlocking the therapeutic potential of direct RAS-GTP inhibition.
Insights
Researchers identified a new treatment for cholangiocarcinoma targeting KRAS mutations. This direct RAS-GTP inhibition offers therapeutic potential for advanced cancers, improving patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Cholangiocarcinoma (bile duct cancer) has dismal outcomes in advanced stages.
- Despite molecular insights, effective treatments for advanced cholangiocarcinoma are limited.
- Oncogenic KRAS mutations occur in 20%-25% of cholangiocarcinoma patients.
Purpose of the Study:
- To explore the therapeutic potential of direct RAS-GTP inhibition in cholangiocarcinoma.
- To identify new treatment strategies for patients with KRAS-mutated cholangiocarcinoma.
Main Methods:
- The study focuses on direct RAS-GTP inhibition strategies.
- Investigated the efficacy of targeting RAS-GTP in preclinical models of cholangiocarcinoma.
Main Results:
- Direct RAS-GTP inhibition demonstrates therapeutic potential in cholangiocarcinoma.
- This approach offers a new avenue for patients with oncogenic KRAS mutations.
Conclusions:
- Targeting RAS-GTP is a promising strategy for cholangiocarcinoma treatment.
- This unlocks new therapeutic possibilities for a subset of advanced cancer patients.
