ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Modulation of splicing factors SF3B1 and SRSF1 by polypurine reverse Hoogsteen hairpins affects the splicing pattern of estrogen receptor α in breast cancer cells.Cancer cell international · 2026Article
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- Identification of prognostic markers related to homologous recombination deficiency in cholangiocarcinoma using CoxBoost and LASSO machine learning techniques.Frontiers in immunology · 2026Article
- DZ-1-artesunate conjugate induces mitochondria-mediated, reactive oxygen species-dependent apoptosis in colorectal cancer tumoroids.Frontiers in pharmacology · 2026Article
- The distinct landscape of tumor immune microenvironment in homologous recombination deficient cancers.Biomarker research · 2025Review
- NADPH oxidase 1/4 dual inhibition impairs transforming growth factor-beta protumorigenic effects in cholangiocarcinoma cancer-associated fibroblasts.Signal transduction and targeted therapy · 2025Article
- Developments and Applications of Liver-on-a-Chip Technology-Current Status and Future Prospects.Biomedicines · 2025Review
- State-of-the-Art Liver Cancer Organoids: Modeling Cancer Stem Cell Heterogeneity for Personalized Treatment.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- DNA damage response mutations enhance the antitumor efficacy of ATR and PARP inhibitors in cholangiocarcinoma cell lines.Oncology letters · 2025Article
- Review
- Utilizing Patient-Derived Xenografts to Model Precision Oncology for Biliary Tract Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Clinical Value of Liquid Biopsy in Patients with FGFR2 Fusion-Positive Cholangiocarcinoma During Targeted Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- SRC inhibition enables formation of a growth suppressive MAGI1-PP2A complex in isocitrate dehydrogenase-mutant cholangiocarcinoma.Science translational medicine · 2024Article
- Article
- Generation of Metastatic Cholangiocarcinoma Patient-Derived Xenograft Models.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Chemotherapy combined with lenvatinib and PD-1 may be a potential better alternative option for advanced unresectable intrahepatic cholangiocarcinoma: a retrospective real-world study.Frontiers in immunology · 2024Article
- The potential of patient-derived organoids in precision medicine of biliary tract cancer.Cell reports. Medicine · 2023Article
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Authors and funding
31 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCholangiocarcinoma (CCA) is usually diagnosed at advanced stages, with limited therapeutic options. Preclinical models focused on unresectable metastatic CCA are necessary to develop rational treatments. Pathogenic mutations in IDH1/2, ARID1A/B, BAP1, and BRCA1/2 have been identified in 30%-50% of patients with CCA. Several types of tumor cells harboring these mutations exhibit homologous recombination deficiency (HRD) phenotype with enhanced sensitivity to PARP inhibitors (PARPi). However, PARPi treatment has not yet been tested for effectiveness in patient-derived models of advanced CCA. EXPERIMENTAL
designWe have established a collection of patient-derived xenografts from patients with unresectable metastatic CCA (CCA_PDX). The CCA_PDXs were characterized at both histopathologic and genomic levels. We optimized a protocol to generate CCA tumoroids from CCA_PDXs. We tested the effects of PARPis in both CCA tumoroids and CCA_PDXs. Finally, we used the RAD51 assay to evaluate the HRD status of CCA tissues.
resultsThis collection of CCA_PDXs recapitulates the histopathologic and molecular features of their original tumors. PARPi treatments inhibited the growth of CCA tumoroids and CCA_PDXs with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1. In line with these findings, only CCA_PDX and CCA patient biopsy samples with mutations of BRCA2 showed RAD51 scores compatible with HRD.
conclusionsOur results suggest that patients with advanced CCA with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1, are likely to benefit from PARPi therapy. This collection of CCA_PDXs provides new opportunities for evaluating drug response and prioritizing clinical trials.
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