The Search for Risk, Diagnostic and Prognostic Biomarkers of Cholangiocarcinoma and their Biological and Clinicopathological Significance

American Journal Of Pathology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Language: Английский

---

Construction and Validation of a T Cell Exhaustion–Related Prognostic Signature in Cholangiocarcinoma

International Journal of Genomics, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Objective: T cell exhaustion (TEX) is a critical determinant of immune resistance. This study was performed to investigate the key genes linked TEX in cholangiocarcinoma (CCA) and construct TEX-associated gene signature forecast prognosis patients with CCA. Methods: Based on expression data acquired from E-MTAB-6389 dataset, TEX-related modules module were identified using weighted coexpression network analysis (WGCNA). Subsequently, prognostic built by univariate least absolute shrinkage selection operator (LASSO) Cox regression analysis. The infiltration each CCA sample evaluated single-sample set enrichment (ssGSEA) package, followed single-cell RNA sequencing (scRNA-seq) Furthermore, experimentally validated cells quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) western blot Results: A total 15 23 identified. Then, four-gene related established, containing Palladin, Cytoskeletal Associated Protein (PALLD), Member RAS Oncogene Family (RAB31), ADAM Metallopeptidase With Thrombospondin Type 1 Motif 2 (ADAMTS2), WISP1, which could predict Moreover, neutrophils, endothelial cells, B exhibited significant samples, these four both significantly positively correlated while negatively neutrophils. 13 types annotated after scRNA-seq Notably, RAB31 mainly highly expressed monocytes, macrophages, DC2 (Dendritic Cells 2), DC3 3), PALLD, ADAMTS2, WISP1 overexpressed fibroblasts. experimental validation revealed that levels RAB31, consistent trend results bioinformatics Conclusion: developed genes, including might be powerful predictor for These

Language: Английский

---

Biomarkers and Management of Cholangiocarcinoma: Unveiling New Horizons for Precision Therapy

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1243 - 1243

Published: April 6, 2025

Cholangiocarcinoma (CCA) is an aggressive malignancy with limited methods for early detection, necessitating the development of reliable biomarkers diagnosis and management. However, conventional tumor markers, such as CA19-9 CEA, exhibit insufficient diagnostic accuracy. Recent advancements in molecular genetics have identified several actionable mutations CCA, enabling molecularly targeted therapies that improve survival patients harboring these genetic alterations. Cancer panels, which facilitate multiplex profiling, are critical identifying mutations. Studies indicate detected CCA cases, receiving mutation-guided achieving markedly better outcomes. Liquid biopsies, including cell-free DNA circulating DNA, offer real-time, non-invasive approaches to monitoring dynamics, heterogeneity, treatment responses. Furthermore, numerous studies non-coding RNAs serum bile promising management CCA. On other hand, immunotherapy, particularly immune checkpoint inhibitors, has shown efficacy subsets patients. success often affected by status microenvironment (TME), underscoring need comprehensive TME analysis predict responses inhibitors. Despite advances, no single biomarker currently demonstrates sufficient sensitivity or specificity clinical application. The integration multi-omics cutting-edge technologies holds promise enhancing accuracy, optimizing stratification, advancing precision medicine These developments highlight transformative potential prognostic assessment, personalized therapeutic interventions

Language: Английский

---

Genomic landscape of biliary tract cancer and corresponding targeted treatment strategies

International Journal of Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Abstract Biliary tract cancers (BTCs) are classified on the basis of their anatomical origin, and feasibility surgical resection depends tumor location extent progression. However, for unresectable BTCs, systemic therapy has been uniformly applied. Gemcitabine cisplatin (GC) GC-based therapies were established as first-line standard BTC treatment. no highly effective second-line established, prognosis remains poor, highlighting need further therapeutic advancements. Meanwhile, era precision medicine expanded use genetic testing, leading to identification actionable molecular targets in BTC. Several targeted therapies, including FGFR inhibitors IDH1 inhibitors, have developed, offering new treatment options potential appropriate cases. Notably, frequency these alterations varies depending location, demonstrating heterogeneity Therefore, it recognized that a tailored approach each patient may be more than uniform therapy. Consequently, although routine testing before initiating is currently limited by medical environment (e.g., cost, accessibility, regional differences), recommended ESMO guideline might increasingly advocated. harbors wide range alterations, numerous being developed accordingly. This review provides an overview reported BTC, frequencies corresponding emphasizing evolving role

Language: Английский

---

Strategies to enhance the response of liver cancer to pharmacological treatments

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 327(1), P. C11 - C33

Published: May 6, 2024

In contrast to other types of cancers, there is no available efficient pharmacological treatment improve the outcomes patients suffering from major primary liver i.e., hepatocellular carcinoma and cholangiocarcinoma. This dismal situation partly due existence in these tumors many different synergistic mechanisms resistance, accounting for lack response patients, not only classical chemotherapy but also more modern agents based on inhibition tyrosine kinase receptors (TKIs) stimulation immune against tumor using checkpoint inhibitors (ICIs). review summarizes efforts develop strategies overcome this severe limitation, including searching novel drugs derived synthetic, semisynthetic, or natural products with vectorial properties therapeutic targets increase drug uptake reduce export cancer cells. Besides, immunotherapy a promising line research that already starting be implemented clinical practice. Although less successful than foreseen future strategy treating cancers considerable. Similarly, epigenetic highly promising. Many “epidrugs,” able act “writer,” “reader,” “eraser” players, are currently being evaluated preclinical studies. Finally, gene therapy broad field fight chemoresistance, impressive advances recently achieved manipulation. sum, although present still dismal, reason hope non-too-distant future.

Language: Английский

---

Splicing, Signaling, and Survival: The Role of RBM39 in Cholangiocarcinoma Progression

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2024, Volume and Issue: unknown, P. 101419 - 101419

Published: Oct. 1, 2024

Language: Английский

---

New Relevant Evidence in Cholangiocarcinoma Biology and Characterization

Cancers, Journal Year: 2024, Volume and Issue: 16(24), P. 4239 - 4239

Published: Dec. 19, 2024

Among solid tumors, cholangiocarcinoma (CCA) emerges as one of the most difficult to eradicate. The silent and asymptomatic nature this tumor, particularly in its early stages, well high heterogeneity at genomic, epigenetic, molecular levels delay diagnosis, significantly compromising efficacy current therapeutic options thus contributing a dismal prognosis. Extensive research has been conducted on pathobiology CCA, recent advances have made classification characterization new targets. Both targeted therapy immunotherapy emerged effective safe strategies for various types cancers, demonstrating potential benefits advanced CCA. Furthermore, deeper comprehension cellular components tumor microenvironment (TME) opened up possibilities innovative treatment methods. This review discusses evidence biology highlighting novel possible druggable

Language: Английский

---