Cholangiocarcinoma

Our multi-omic analysis provides new insight into molecular underpinnings of CHOL and identifies candidate disease drivers, signaling pathways and herbal targets for further validation. This systematic approach established a framework for illuminating causal links between genetics, molecular mechanisms and disease pathogenesis, with potential to accelerate drug and biomarker development for CHOL.

In conclusion, candidate cir-miRNAs have been identified as potential biomarkers including miR-423-5p, miR-93-5p and miR-4532. Screening by miR-4532 and confirmed with miR-423-5p, miR-93-5p were suggested for differential CCA patients in the endemic area of O. viverrini.

Our findings not only provide a reliable imaging-based screening platform for evaluating glycocalyx-targeting pharmacological interventions but also offer mechanistic insights into how CCA may avoid immune elimination through fortification of the glycocalyx layer with mucins. Additionally, this work presents a novel therapeutic strategy for mucin-overexpressing cancers, potentially improving immunotherapy efficacy across various cancer types.

P=N/A, N=60, Not yet recruiting, Nantes University Hospital

P=N/A, N=10000, Recruiting, Target PharmaSolutions, Inc. | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

The responsiveness of gastrointestinal stromal tumors to imatinib requires validation via molecular testing. Patients diagnosed with pancreatic cancer may see enhanced survival rates by targeted therapy addressing microsatellite instability and BRCA mutations. In bile duct malignancies, especially intrahepatic cholangiocarcinoma of the small duct variant, the analysis of IDH1 mutations and FGFR2 fusions presents new treatment prospects.

Based on network analysis and the summary of previous studies, it was proposed that CHOL tumor cells secrete CXCL5, leading to neutrophil recruitment to the tumor microenvironment. Vascular endothelial growth factor A (VEGFA) released by the infiltrating neutrophils is suggested to promote overexpression of WNK1 by tumor cells, activating the VEGFA downstream pathway to promote angiogenesis and tumor progression.

TAM promotes CCA progression and chemoresistance through activating OSM-Yap-ID1.

In addition, we also found that HY-PDT inhibit cholangiocarcinoma cells migration and the EMT process by inhibiting the AKT/mTORC1 pathway. Our study illustrated a new mechanism of action for HY-PDT and might throw light on the individualized precision therapy for cholangiocarcinoma patients.

In this largest and most systematic analysis of acquired resistance to an FGFR inhibitor from prospective clinical trials, emergence of secondary FGFR2 kinase domain mutations was observed in most patients receiving clinical benefit to futibatinib. ctDNA analysis shows clinically relevant potential as a noninvasive method for assessing genomic profiles, identifying patients who may benefit from FGFR inhibitor treatment, and exploring acquired resistance mechanisms.

This study identifies CXCL5 and SLC6A14 as key biomarkers of MVI, highlighting their roles in tumor proliferation, immune resistance, and poor clinical outcomes. These findings provide valuable insights into the spatial organization of MVI and its contribution to ICC progression, offering potential therapeutic targets.

P2, N=80, Recruiting, Lisata Therapeutics, Inc. | Trial completion date: Dec 2025 --> Mar 2026 | Trial primary completion date: Dec 2025 --> Mar 2026

P=N/A, N=261, Completed, University of Pittsburgh | Phase classification: P3 --> P=N/A

P2, N=2, Terminated, University Health Network, Toronto | N=30 --> 2 | Trial completion date: Jan 2029 --> Dec 2024 | Recruiting --> Terminated | Trial primary completion date: Jan 2026 --> Dec 2024; Low accrual

FAP is expressed in the stroma of a high proportion (93%) of primary CCA independent of patient clinical or tumor pathology features. As such, these data provide the tissue basis for systematically evaluating FAP as a theranostic target across a broad range of CCA subtypes.

P1/2, N=42, Recruiting, Medigen Biotechnology Corporation

P=N/A, N=100, Recruiting, iOMEDICO AG | Not yet recruiting --> Recruiting

P2, N=100, Not yet recruiting, Beijing Biostar Pharmaceuticals Co., Ltd.

ASAP1 regulates Wnt/β-catenin pathway activity in CC, promoting cell migration, and invasion in culture; and promotes tumor development in vivo. ASAP1 plays a key role in EHCC tumor development and could serve as a potential therapeutic target for EHCC.

P2, N=38, Not yet recruiting, Mehmet Akce

P=N/A, N=300, Active, not recruiting, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

P=N/A, N=146, Recruiting, Tianjin Medical University Cancer Institute and Hospital | N=80 --> 146

Our case report strengthens the evidence that crizotinib may be a viable treatment option for patients with ICC with a c-MET tyrosine kinase fusion, necessitating additional clinical investigation.

P1, N=124, Not yet recruiting, MacroGenics

P1, N=48, Completed, Symphogen A/S | Active, not recruiting --> Completed

The symptoms were reversible and tended to improve after withdrawal of entrectinib. It is crucial to increase awareness of TRKi-specific adverse events and their proper management.

The patient was treated with pemigatinib (a selective FGFR inhibitor) in combination with Gemcitabine and Cisplatin at our hospital. To the best of our knowledge, this is the first reported rare case of unresectable cHCC-CCA with FGFR2-PRDM16 fusion in a child successfully treated with a combination of pemigatinib and chemotherapy as a first-line regimen. This treatment combination may be effective and safe for patients with unresectable cHCC-CCAs.

No abstract available

The adverse impact of KRAS mutations in BTC is driven by G12 alterations in patients with IHC regardless of resection status, which was not observed in GB or EHC. There are unique comutational partners in distinct BTC subsets. These differences have important clinical implications in the era of KRAS-targeted therapeutics.

Furthermore, STAT5a knockdown counteracted the effects of inhibition of SNHG3 and miR-151a-3p on the aggressive behavior of CAA. SNHG3 promotes CCA progression via the miR-151a-3p/STAT5a axis, providing novel insights into the clinical treatment of CCA.

Patients with LAPCCA frequently tolerate induction gemcitabine-cisplatin, leading to a 26% resection rate with 40 months overall survival. These findings support routine re-staging after three to six cycles of palliative treatment, and lay the groundwork for future prospective trials in this patient group.

The nomogram model, incorporating key risk factors for cholangiocarcinoma patients post-immune therapy, demonstrates robust predictive accuracy for survival outcomes, offering the potential for improved clinical decision-making.

P=N/A, N=32, Recruiting, Azienda Ospedaliera di Padova

P1, N=130, Active, not recruiting, Celldex Therapeutics | Recruiting --> Active, not recruiting | Trial completion date: Feb 2026 --> May 2025 | Trial primary completion date: Dec 2024 --> May 2025

P1/2, N=53, Active, not recruiting, Medivir | Trial completion date: Feb 2024 --> Jun 2025 | Trial primary completion date: Feb 2024 --> Dec 2024

P=N/A, N=60, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2025 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2027

P2, N=70, Recruiting, Tianjin Medical University Cancer Institute and Hospital

Surgical resection is the mainstay of multidisciplinary treatment for PHCC and IHCC. In advanced stages of IHCC, the combination of loco-regional therapies and repeat surgery, along with the enhanced efficacy of systemic chemotherapy, plays a significant role in a patient's survival.

P2, N=100, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

P2, N=110, Active, not recruiting, Tianjin Medical University Cancer Institute and Hospital

P=N/A, N=300, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

Currently, pemigatinib and futibatinib are FDA approved FGFR-targeted therapies that have demonstrated remarkable responses. Additionally, unique side effects of FGFR inhibitors may limit their efficacy in clinical practice and can have detrimental effects on quality of life. Several novel FGFR inhibitors are currently being investigated to overcome resistance mechanisms and reduce toxicities.