Opening and changing: mammalian SWI/SNF complexes in organ development and carcinogenesis DOI Creative Commons

Fadia Abu Sailik,

Bright Starling Emerald, Suraiya A. Ansari

et al.

Open Biology, Journal Year: 2024, Volume and Issue: 14(10)

Published: Oct. 1, 2024

The switch/sucrose non-fermentable (SWI/SNF) subfamily are evolutionarily conserved, ATP-dependent chromatin-remodelling complexes that alter nucleosome position and regulate a spectrum of nuclear processes, including gene expression, DNA replication, damage repair, genome stability tumour suppression. These complexes, through their chromatin remodelling, contribute to the dynamic regulation genetic information maintenance cellular processes essential for normal function overall genomic integrity. Mutations in SWI/SNF subunits detected 25% human malignancies, indicating efficient functioning this complex is required prevent tumourigenesis diverse tissues. During development, help establish maintain expression patterns proper identity function, lineage-specific enhancers. Moreover, specific molecular signatures associated with mutations, disruption activity at enhancers, evasion G0 cell cycle arrest, induction plasticity pro-oncogene activation Polycomb group (PcG) antagonism, linked initiation progression carcinogenesis. Here, we review insights into aetiology malignancies driven by correlate these mechanisms developmental functions. Finally, discuss therapeutic potential targeting cancer.

Language: Английский

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: An early exploratory analysis of real‐world data DOI Creative Commons
Margherita Rimini, Lorenzo Fornaro, Sara Lonardi

et al.

Liver International, Journal Year: 2023, Volume and Issue: 43(8), P. 1803 - 1812

Published: July 14, 2023

Abstract Background The TOPAZ‐1 phase III trial reported a survival benefit with the anti‐programmed death cell ligand 1 (anti‐PD‐L1) durvalumab in combination gemcitabine and cisplatin patients advanced biliary tract cancer. present study investigated efficacy safety of this new standard treatment real‐world setting. Methods analysed population included unresectable, locally or metastatic adenocarcinoma treated at 17 Italian centres. primary endpoint was progression‐free (PFS), whereas secondary endpoints overall (OS), response rate (ORR) safety. Unadjusted adjusted hazard ratios (HRs) by baseline characteristics were calculated using Cox proportional hazards model. Results From February 2022 to November 2022, 145 enrolled. After median follow‐up 8.5 months (95% CI: 7.9–13.6), PFS 8.9 7.4–11.7). Median OS 12.9 10.9–12.9). investigator‐assessed confirmed ORR 34.5%, disease control 87.6%. Any grade adverse events (AEs) occurred 137 (94.5%). Grades 3–4 AEs 51 (35.2%). immune‐mediated (imAEs) 22.7%. imAEs 2.1% patients. In univariate analysis, non‐viral aetiology, ECOG PS >0 NLR ≥3 correlated shorter PFS. Conclusion results first analysis mostly achieved terms PFS,

Language: Английский

Citations

63
Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: A large real-life worldwide population DOI
Margherita Rimini, Lorenzo Fornaro, Mario Domenico Rizzato

et al.

European Journal of Cancer, Journal Year: 2024, Volume and Issue: 208, P. 114199 - 114199

Published: June 30, 2024

Language: Английский

Citations

12
Durvalumab Plus Gemcitabine and Cisplatin Versus Gemcitabine and Cisplatin in Biliary Tract Cancer: a Real-World Retrospective, Multicenter Study DOI
Margherita Rimini, Gianluca Masi, Sara Lonardi

et al.

Targeted Oncology, Journal Year: 2024, Volume and Issue: 19(3), P. 359 - 370

Published: May 1, 2024

Language: Английский

Citations

10
Different Genomic Clusters Impact on Responses in Advanced Biliary Tract Cancer Treated with Cisplatin Plus Gemcitabine Plus Durvalumab DOI
Margherita Rimini, Eleonora Loi, Mario Domenico Rizzato

et al.

Targeted Oncology, Journal Year: 2024, Volume and Issue: 19(2), P. 223 - 235

Published: Feb. 12, 2024

Language: Английский

Citations

5
Recent progress in emerging molecular targeted therapies for intrahepatic cholangiocarcinoma DOI
Younghoon Kim, Jaewon Song, Namkyoung Kim

et al.

RSC Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Small-molecule and antibody-based targeted therapies for intrahepatic cholangiocarcinoma (iCCA): addressing promising oncogenic molecular alterations, including IDH1, FGFR2, BRAF, HER2, the PD-1/PD-L1 axis.

Language: Английский

Citations

0
A MiR181/Sirtuin1 regulatory circuit modulates drug response in biliary cancers DOI Creative Commons
Anna Barbato,

Fabiola Piscopo,

Massimiliano Salati

et al.

Clinical and Experimental Medicine, Journal Year: 2024, Volume and Issue: 24(1)

Published: April 10, 2024

Abstract Despite recent advances, biliary tract cancer (BTC) remains one of the most lethal tumor worldwide due to late diagnosis, limited therapeutic strategies and resistance conventional therapies. In years, high-throughput technologies have enabled extensive genome, transcriptome sequencing unveiling, among others, regulatory potential microRNAs (miRNAs). Compelling evidence shown that miRNA are attractive targets promising candidates as biomarkers for various therapy-resistant tumors. The analysis profile successfully identified miR-181c -181d significantly downregulated in BTC patients. Low expression levels were correlated with worse prognosis poor treatment efficacy. fact, progression-free survival indicated rates low expressing cell lines revealed both miRNAs dysregulated. Functional vitro experiments showed overexpression affected viability increased sensitivity chemotherapy compared controls. addition, by using bioinformatic tools we miR-181c/d functional role is determined binding their target SIRT1 (Sirtuin 1). Moreover, patients high miR-181 an improved response. An integrative network demonstrated that, miR-181/SIRT1 circuit had a effect on several important metabolic tumor-related processes. Our study act suppressor BTC, suggesting use strategy resistant cancers predictive biomarker precision medicine BTC.

Language: Английский

Citations

3
IDH Mutant Cholangiocarcinoma: Pathogenesis, Management, and Future Therapies DOI Creative Commons
Alexander W. Bray, Vaibhav Sahai

Current Oncology, Journal Year: 2025, Volume and Issue: 32(1), P. 44 - 44

Published: Jan. 17, 2025

Mutations in isocitrate dehydrogenase (IDH) genes are among the most frequently encountered molecular alterations cholangiocarcinoma (CCA). These neomorphic point mutations endow mutant IDH (mIDH) with ability to generate an R-enantiomer of 2-hydroxyglutarate (R2HG), a metabolite that drives malignant transformation through aberrant epigenetic signaling. As result, pharmacologic inhibition mIDH has become attractive therapeutic strategy CCAs harboring this mutation. One such inhibitor, ivosidenib, already undergone clinical validation and received FDA approval disease, but there is still much work be done improve outcomes CCA patients. In publication we will review pathogenesis treatment special emphasis on novel agents combinations currently under investigation.

Language: Английский

Citations

0
Updated survival outcomes with ivosidenib in patients with previously treated IDH1-mutated intrahepatic-cholangiocarcinoma: an Italian real-world experience DOI Creative Commons
Margherita Rimini, Valentina Burgio, Lorenzo Antonuzzo

et al.

Therapeutic Advances in Medical Oncology, Journal Year: 2023, Volume and Issue: 15

Published: Jan. 1, 2023

The results of the phase III ClarIDHy trial led to FDA approval ivosidenib as a therapeutic option for patients with locally advanced or metastatic cholangiocarcinoma (CCA) harboring isocitrate dehydrogenase 1 (IDH1) mutations. We recently published first data on use in real-world setting.Here we report updated survival 11 IDH1-mutated CCA who received clinical practice.Patients treated second- and third-line treatments have been collected aim evaluate outcomes. A molecular study has performed by next generation sequencing essay.Overall, were included. After median follow-up 13.7 months, progression-free from start treatment was 4.4 months (95% CI: 2.0-5.8), whereas overall 15 6.6-15.0) regardless line. Disease control rate 63%, two achieving partial response (18%). Eighteen percent experienced at least one treatment-related adverse events (AEs), but no grade ⩾3 reported. most frequently observed 2 AEs prolonged QT interval hypomagnesemia. profiling 8 out patients, highlighting TP53, BAP1, CDKN2A, CDKN2B common co-altered genes these patients.The present update confirms our previous experience CCA. Real-world evidence larger numbers is needed confirm findings.

Language: Английский

Citations

8
Clinical Outcomes After Progression on First-Line Therapies in IDH1 Mutated Versus Wild-Type Intrahepatic Cholangiocarcinoma Patients DOI
Margherita Rimini, Carles Fabregat-Franco, Mara Persano

et al.

Targeted Oncology, Journal Year: 2023, Volume and Issue: 18(1), P. 139 - 145

Published: Jan. 1, 2023

Language: Английский

Citations

6
PLK1 and its substrate MISP facilitate intrahepatic cholangiocarcinoma progression by promoting lymphatic invasion and impairing E-cadherin adherens junctions DOI Creative Commons
Yi‐Ru Pan,

Joseph Chieh‐Yu Lai,

Wen‐Kuan Huang

et al.

Cancer Gene Therapy, Journal Year: 2023, Volume and Issue: 31(2), P. 322 - 333

Published: Dec. 6, 2023

Abstract Intrahepatic cholangiocarcinoma (iCCA) is a subtype of CCA and has high mortality rate relatively poor prognosis. However, studies focusing on increased cell motility loss epithelial integrity during iCCA progression remain scarce. We collected seven fresh tumor samples from four patients to perform RNA sequencing (RNA-seq) assay for transposase-accessible chromatin using (ATAC-seq) determine the transcriptome profile accessibility iCCA. The expression cycle regulators, including PLK1 its substrate MISP, was identified. Ninety-one were used validate clinical significance MISP. upregulation MISP determined in tissues. Increased significantly correlated with number, N stage, lymphatic invasion an cohort. Knockdown or reduced trans-lymphatic endothelial migration wound healing affected focal adhesions vitro. In cell‒cell junctions, localized adherens junctions suppressed E-cadherin dimerization. disrupted myosin-dependent manner. Furthermore, promoted proliferation vitro tumorigenesis vivo. iCCA, promote aggressiveness by increasing invasion, growth, through repression junctions.

Language: Английский

Citations

4