Identification of Transcriptional Regulators of Immune Evasion Across Cancers: An Alternative Immunotherapeutic Strategy for Cholangiocarcinoma DOI Open Access
Simran Venkatraman, Brinda Balasubramanian, Pornparn Kongpracha

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(24), P. 4197 - 4197

Published: Dec. 17, 2024

Background: Cancer immune evasion is a multifaceted process that synchronizes pro-tumoral infiltration, immunosuppressive inflammation, and inhibitory checkpoint expression (IC). Current immunotherapies combat this issue by reinstating immunosurveillance of tumors; however, it benefits limited patient population. Thus, more effective immunotherapeutic strategy warranted to cater specific populations. This investigation introduces novel via inhibition master regulators (MR-IE). Methods: Samples the TCGA Pan-Cancer Atlas transcriptomic data were subset stratified based on IC estimated cell infiltration. Transcriptomic analysis was conducted unravel pathways associated with process. Transcription factor enrichment survival analyses identify rank candidate MR-IEs per cancer type. Results: Inhibition top-ranking MR-IE cholangiocarcinoma (CCA), MYC, modulated gene protein PD-L1. Moreover, inflammatory markers, IFNA21 CX3CL1, downregulated, anti-tumoral cytokines, IL-18 IL-16, upregulated. Lastly, MYC potentiated fourth-generation anti-folate receptor alpha (FRα) CAR-T therapy against CCA cells. Conclusions: Cumulatively, study highlights promise as potent for treatment offers list type further validation.

Language: Английский

New trends in diagnosis and management of gallbladder carcinoma DOI Open Access
Efstathios Pavlidis, I. Galanis, T. Pavlidis

et al.

World Journal of Gastrointestinal Oncology, Journal Year: 2024, Volume and Issue: 16(1), P. 13 - 29

Published: Jan. 9, 2024

Gallbladder (GB) carcinoma, although relatively rare, is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis. It closely associated cholelithiasis long-standing large (> 3 cm) gallstones in up to 90% of cases. The other main predisposing factors for GB carcinoma include molecular such as mutated genes, wall calcification (porcelain) or mainly mucosal microcalcifications, polyps ≥ 1 cm size. Diagnosis made by ultrasound, computed tomography (CT), and, more precisely, magnetic resonance imaging (MRI). Preoperative staging great importance decision-making regarding therapeutic management. based on MRI findings, leading technique liver metastasis imaging, enhanced three-phase CT angiography, angiography major vessel assessment. also necessary use positron emission (PET)-CT 18F-FDG PET-MRI accurately detect metastases any occult deposits active metabolic uptake. Staging laparoscopy may dissemination not otherwise found 20%-28.6% Multimodality treatment needed, including surgical resection, targeted therapy biological agents according testing gene mapping, chemotherapy, radiation therapy, immunotherapy. understand updated guidelines current options. extent intervention depends disease stage, ranging from simple cholecystectomy (T1a) extended resections (T1b), wide lymph node resection every case IV-V segmentectomy (T2), hepatic trisegmentectomy hepatectomy accompanied hepaticojejunostomy Roux-Y, adjacent organ if (T3). Laparoscopic robotic surgery shows fewer postoperative complications equivalent oncological outcomes when compared open surgery, but much attention must be paid avoiding injuries. In addition novel along immunotherapy recent improvements radiotherapy chemotherapy (neoadjuvant-adjuvant capecitabine, cisplatin, gemcitabine) have yielded promising results even inoperable cases calling palliation (T4). Thus, individualized applied.

Language: Английский

Citations

13
Current Status of Targeted Therapy for Biliary Tract Cancer in the Era of Precision Medicine DOI Open Access
Takafumi Mie, Takashi Sasaki, Takeshi Okamoto

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(5), P. 879 - 879

Published: Feb. 22, 2024

First-line chemotherapy has been established for advanced biliary tract cancer (BTC). However, few treatment options are available as second-line treatment. Advances in comprehensive genomic analysis revealed that nearly half of patients with BTC harbor targetable genetic alterations such fibroblast growth factor receptor (FGFR), isocitrate dehydrogenase (IDH), BRAF, human epidermal 2 (HER2), microsatellite instability (MSI)-high, neurotrophic tropomyosin kinase (NTRK), rearranged during transfection (RET), and poly (adenosine diphosphate-ribose) polymerase (PARP). This review summarizes currently precision medicine clinical trials BTC.

Language: Английский

Citations

4
Overcoming Resistance to Immune Checkpoint Blockade in Liver Cancer with Combination Therapy: Stronger Together? DOI Creative Commons

Wiebke Werner,

Maria Kuzminskaya,

Isabella Lurje

et al.

Seminars in Liver Disease, Journal Year: 2024, Volume and Issue: 44(02), P. 159 - 179

Published: May 1, 2024

Primary liver cancer, represented mainly by hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA), is one of the most common deadliest tumors worldwide. While surgical resection or transplantation are best option in early disease stages, these often present advanced stages systemic treatment required to improve survival time. The emergence immune checkpoint inhibitor (ICI) therapy has had a positive impact especially on cancers, thereby establishing immunotherapy as part first-line HCC CCA. Nevertheless, low response rates reflect usually cold immunosuppressed tumor microenvironment primary cancer. In this review, we aim summarize mechanisms resistance leading escape with special focus composition both CCA, also reflecting recent important developments ICI combination therapy. Furthermore, discuss how ICIs established cancer treatments (e.g. multikinase inhibitors chemotherapy) well more complex combinations state-of-the-art therapeutic concepts may reshape microenvironment, higher long-lasting antitumor immunity for patients.

Language: Английский

Citations

4
Biomarkers for the Evaluation of Immunotherapy in Patients with Cholangiocarcinoma DOI Open Access

Thaleia-Eleftheria Bousou,

Panagiotis Sarantis, Ioanna A. Anastasiou

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(3), P. 555 - 555

Published: Feb. 6, 2025

Cholangiocarcinoma is a rare primary liver cancer with poor prognosis, due to the advanced stage at time of diagnosis and limited therapeutic options, response. Chemotherapy remains standard first-line treatment, but advent immunotherapy has recently induced promising results. Given fact that frequency increasing nowadays survival rate very low, it crucial recognize patients who are suitable for will have best Different types biomarkers, such as interleukins, exosomes, mi-RNA, ctDNA, gene mutations, been studied their feasibility, not only early biliary tract also determination responsiveness in treatment. Less frequently, these studies focus on finding observing biomarkers receive immunotherapy. This review aims summarize current knowledge existing/promising unresectable or metastatic cholangiocarcinoma, treated monotherapy, combined chemotherapy.

Language: Английский

Citations

0
Bispecific antibodies (bsAbs) directed against PD-1/PD-L1 and CTLA-4; a mini review DOI Creative Commons
Amirhossein Mardi, Leili Aghebati‐Maleki

Human Antibodies, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Novel approaches to tumor immunotherapy include adoptive cell immunotherapy, immune checkpoint inhibitors (ICIs), and bispecific antibodies (bsABs). bsABs are members of the antibody family that have ability distinguish between two distinct antigens or epitopes on a single antigen. These show better clinical results than monoclonal antibodies, suggesting they might be useful choice for immunotherapy. Additionally, dual blockade targeting PD-1/PD-L1 CTLA-4 functions at various phases T activation with synergistically increasing responses against cancer cells, in contrast ICI monotherapy, which sometimes displays treatment resistance limited effectiveness. It has been shown response rates anti-tumor effects may increased synergistic manner by ICI-based combination therapy. We explore safety effectiveness ICIs (especially PD1/PDL1 CTLA-4) treatments this study goal offering evidence-based methods research tailored identification management.

Language: Английский

Citations

0
Health-related quality of life in participants with advanced biliary tract cancer from the randomized phase III KEYNOTE-966 study DOI
Changhoon Yoo, Makoto Ueno, Heinz‐Josef Klümpen

et al.

Journal of Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Systemic therapy with pemigatinib and sintilimab followed by resection for recurrent FGFR-2-positive intrahepatic cholangiocarcinoma: a case report DOI Creative Commons
Yuchen Yang, Jingfeng Li, Di Ma

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: April 4, 2025

Background Fibroblast growth factor receptor-2 (FGFR-2) mutations are frequently observed in intrahepatic cholangiocarcinoma (ICC). While FGFR2-targeted therapies primarily studied advanced ICC, this report presents a rare case of locally recurrent ICC treated with systemic therapy, leading to significant tumor regression and successful R0 resection. Case presentation A 51-year-old female underwent right posterior hepatectomy cholecystectomy 2018 for ICC. In August 2022, postoperative MRI revealed recurrence near the hepatic vein, accompanied by bile duct dilation thrombus. Given tumor’s proximity critical structures confirmed FGFR-2 fusion, therapy pemigatinib sintilimab was initiated. After four cycles, showed partial remission, reduction May 2023, patient hemi-hepatectomy. Postoperatively, she continued combination without or metastasis 19 months. Conclusion This highlights efficacy pemigatinib-based achieving enabling curative resection FGFR-2-positive The outcome underscores potential targeted managing warranting further investigation.

Language: Английский

Citations

0
Cisplatin-induced Disruption of Mitochondrial Divisome Leads to Enhanced Cisplatin Resistance in Cholangiocarcinoma DOI Creative Commons
Guoyue Lv,

Wentao Mu,

Yan‐Nan Cao

et al.

Journal of Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Treatment resistance in pancreatic and biliary tract cancer: molecular and clinical pharmacology perspectives DOI Creative Commons
Belén Toledo, Chiara Deiana,

Fabio Scianò

et al.

Expert Review of Clinical Pharmacology, Journal Year: 2024, Volume and Issue: 17(4), P. 323 - 347

Published: Feb. 28, 2024

Introduction Treatment resistance poses a significant obstacle in oncology, especially biliary tract cancer (BTC) and pancreatic (PC). Current therapeutic options include chemotherapy, targeted therapy, immunotherapy. Resistance to these treatments may arise due diverse molecular mechanisms, such as genetic epigenetic modifications, altered drug metabolism efflux, changes the tumor microenvironment. Identifying overcoming mechanisms is major focus of research: strategies being explored combination therapies, modulation microenvironment, personalized approaches.

Language: Английский

Citations

3
Immune checkpoint inhibitors and the liver: balancing therapeutic benefit and adverse events DOI
Eléonora De Martin, Claudia Angela Maria Fulgenzi, Ciro Celsa

et al.

Gut, Journal Year: 2024, Volume and Issue: unknown, P. gutjnl - 332125

Published: Dec. 10, 2024

Immune checkpoint inhibitors (ICI) have led to breakthrough improvements in the management of malignancy including hepatocellular (HCC) and biliary tract cancer, improving decades-old standards care increasing patient survival. In both liver tumour types, which commonly arise context inflammation underlying functional impairment, lack validated predictors response underscores need balance predicted gains survival with risk treatment-related hepatoxicity decompensation chronic disease.In addition, is implicated toxicity associated ICI therapy for non-liver cancers, exhibits a high degree variability presentation severity. An accurate assessment mandatory diagnosis ICI-induced injury.In this Recent Advances article, we provide an overview mechanisms efficacy anticancer immunotherapy tumours extrahepatic malignancies.We compare contrast characteristics, strategies outcomes from immune-related injury patients hepatitis/cirrhosis or healthy discuss latest findings on how may impact outlook malignancies offering insights into future directions clinical research practice field.

Language: Английский

Citations

3