ArticleCell death & disease2019
MEK inhibition suppresses K-Ras wild-type cholangiocarcinoma in vitro and in vivo via inhibiting cell proliferation and modulating tumor microenvironment.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Targeting the 4EBP1/HSP90β/Nrf2 Axis Sensitizes β-catenin-mutant Hepatocellular Carcinoma to mTOR Inhibitors via Ferroptosis Induction.Journal of clinical and translational hepatology · 2026Article
- RPLP1 Is Up-Regulated in Human Adenomyosis and Endometrial Adenocarcinoma Epithelial Cells and Is Essential for Cell Survival and Migration In Vitro.International journal of molecular sciences · 2023Article
- Kinome profiling of cholangiocarcinoma organoids reveals potential druggable targets that hold promise for treatment stratification.Molecular medicine (Cambridge, Mass.) · 2022Article
- In Vivo Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma.Cancer research · 2022Article
- MiR-155-5p suppresses SOX1 to promote proliferation of cholangiocarcinoma via RAF/MEK/ERK pathway.Cancer cell international · 2021Article
- Computational Analysis of Cholangiocarcinoma Phosphoproteomes Identifies Patient-Specific Drug Targets.Cancer research · 2021Article
- Alpelisib combination treatment as novel targeted therapy against hepatocellular carcinoma.Cell death & disease · 2021Article
- Anti-PD-1 in Combination With Trametinib Suppresses Tumor Growth and Improves Survival of Intrahepatic Cholangiocarcinoma in Mice.Cellular and molecular gastroenterology and hepatology · 2021Article
- MEK Inhibition: A New Ally in Immunotherapy for Intrahepatic Cholangiocarcinoma.Cellular and molecular gastroenterology and hepatology · 2021Article
- Inhibitor 9 Combined With Androgen Deprivation Therapy or Chemotherapy Delays the Malignant Behavior of Castration-Resistant Prostate Cancer Through K-Ras/PLCε/PKCε Signaling Pathway.Frontiers in oncology · 2020Article
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Authors and funding
15 authors at 5 institutions in 3 countries.
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Abstract
PD901, a MEK inhibitor, has been demonstrated of therapeutic efficacy against cholangiocarcinoma (CCA) harboring K-Ras oncogenic mutations. However, most CCA exhibit no K-Ras mutations. In the current study, we investigated the therapeutic potential of PD901, either alone or in combination with the pan-mTOR inhibitor MLN0128, for the treatment of K-Ras wild-type CCA in vitro using human CCA cell lines, and in vivo using AKT/YapS127A CCA mouse model. We discovered that in vitro, PD901 treatment strongly inhibited CCA cell proliferation, and combined PD901 and MLN0128 therapy further increased growth inhibition. In vivo, treatment of PD901 alone triggered tumor regression, which was not further increased when the two drugs were administered simultaneously. Mechanistically, PD901 efficiently hampered ERK activation in vitro and in vivo, leading to strong inhibition of CCA tumor cell cycle progression. Intriguingly, we discovered that PD901, but not MLN0128 treatment resulted in changes affecting the vasculature and cancer-associated fibroblasts in AKT/YapS127A mouse lesions. It led to the decreased hypoxia within tumor lesions, which may further enhance the anti-cell proliferation activities of PD901. Altogether, our study demonstrates that MEK inhibitors could be effective for the treatment of K-Ras wild-type CCA via inhibiting cell proliferation and modulating tumor microenvironment.
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