ArticleCancer research2022
In Vivo Modeling of Patient Genetic Heterogeneity Identifies New Ways to Target Cholangiocarcinoma.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Criteria for preclinical models of cholangiocarcinoma: scientific and medical relevance.Nature reviews. Gastroenterology & hepatology · 2023Guideline
- Advances in the Molecular Mechanisms of Cholangiocarcinoma: A Comprehensive Review of Biomarkers, Regulatory Pathways and Tumor Microenvironment Reprogramming.International journal of molecular sciences · 2026Review
- Cholangiocarcinoma 2026: status quo, unmet needs and priorities.Nature reviews. Gastroenterology & hepatology · 2026Review
- Single-cell multi-omics in biliary tract cancers: decoding heterogeneity, microenvironment, and treatment strategies.Molecular biomedicine · 2025Review
- Syngeneic murine models with distinct immune microenvironments represent subsets of human intrahepatic cholangiocarcinoma.Journal of hepatology · 2024Article
- The histone lysine acetyltransferase KAT2B inhibits cholangiocarcinoma growth: evidence for interaction with SP1 to regulate NF2-YAP signaling.Journal of experimental & clinical cancer research : CR · 2024Article
- A TGFβ-ECM-integrin signaling axis drives structural reconfiguration of the bile duct to promote polycystic liver disease.Science translational medicine · 2023Article
- NOTCH signalling - a core regulator of bile duct disease?Disease models & mechanisms · 2023Review
- DKK1 drives immune suppressive phenotypes in intrahepatic cholangiocarcinoma and can be targeted with anti-DKK1 therapeutic DKN-01.Liver international : official journal of the International Association for the Study of the Liver · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy of the bile ducts within the liver characterized by high levels of genetic heterogeneity. In the context of such genetic variability, determining which oncogenic mutations drive ICC growth has been difficult, and developing modes of patient stratification and targeted therapies remains challenging. Here we model the interactions between rare mutations with more common driver genes and combine in silico analysis of patient data with highly multiplexed in vivo CRISPR-spCas9 screens to perform a functional in vivo study into the role genetic heterogeneity plays in driving ICC. Novel tumor suppressors were uncovered, which, when lost, cooperate with the RAS oncoprotein to drive ICC growth. Focusing on a set of driver mutations that interact with KRAS to initiate aggressive, sarcomatoid-type ICC revealed that tumor growth relies on Wnt and PI3K signaling. Pharmacologic coinhibition of Wnt and PI3K in vivo impeded ICC growth regardless of mutational profile. Therefore, Wnt and PI3K activity should be considered as a signature by which patients can be stratified for treatment independent of tumor genotype, and inhibitors of these pathways should be levied to treat ICC. SIGNIFICANCE: This work shows that, despite significant genetic heterogeneity, intrahepatic cholangiocarcinoma relies on a limited number of signaling pathways to grow, suggesting common therapeutic vulnerabilities across patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.