An Optimized NGS Workflow Defines Genetically Based Prognostic Categories for Patients with Uveal Melanoma DOI Creative Commons
Michele Massimino, Elena Tirrò, Stefania Stella

и другие.

Biomolecules, Год журнала: 2025, Номер 15(1), С. 146 - 146

Опубликована: Янв. 18, 2025

Background: Despite advances in uveal melanoma (UM) diagnosis and treatment, about 50% of patients develop distant metastases, thereby displaying poor overall survival. Molecular profiling has identified several genetic alterations that can stratify with UM into different risk categories. However, these are currently dispersed over multiple studies methodologies, emphasizing the need for a defined workflow will allow standardized reproducible molecular analyses. Methods: Following findings published by “The Cancer Genome Atlas–UM” (TCGA-UM) study, we developed an NGS-based gene panel (called UMpanel) classifies mutation sets four categories: initiating (CYSLTR2, GNA11, GNAQ PLCB4), prognostic (BAP1, EIF1AX, SF3B1 SRSF2), emergent biomarkers (CDKN2A, CENPE, FOXO1, HIF1A, RPL5 TP53) chromosomal abnormalities (imbalances chromosomes 1, 3 8). Results: Employing commercial panels, reference mutated DNAs Sanger sequencing, performed comparative analysis found our methodological approach successfully predicted survival great specificity sensitivity compared to TCGA-UM cohort was used as validation group. Conclusions: Our results demonstrate translates reliable tool clinical stratification UM.

Язык: Английский

Environmental effects of stratospheric ozone depletion, UV radiation, and interactions with climate change: UNEP Environmental Effects Assessment Panel, Update 2020 DOI Creative Commons
Rachel Ε. Neale, Paul W. Barnes,

T. Matthew Robson

и другие.

Photochemical & Photobiological Sciences, Год журнала: 2021, Номер 20(1), С. 1 - 67

Опубликована: Янв. 1, 2021

Abstract This assessment by the Environmental Effects Assessment Panel (EEAP) of United Nations Environment Programme (UNEP) provides latest scientific update since our most recent comprehensive (Photochemical and Photobiological Sciences, 2019, 18, 595–828). The interactive effects between stratospheric ozone layer, solar ultraviolet (UV) radiation, climate change are presented within framework Montreal Protocol Sustainable Development Goals. We address how these global environmental changes affect atmosphere air quality; human health; terrestrial aquatic ecosystems; biogeochemical cycles; materials used in outdoor construction, energy technologies, fabrics. In many cases, there is a growing influence from seasonality extreme events due to change. Additionally, we assess transmission severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which responsible for COVID-19 pandemic, context linkages with UV radiation Protocol.

Язык: Английский

Процитировано

173
Melanoma models for the next generation of therapies DOI Creative Commons
E. Elizabeth Patton, Kristen L. Mueller, David J. Adams

и другие.

Cancer Cell, Год журнала: 2021, Номер 39(5), С. 610 - 631

Опубликована: Фев. 5, 2021

Язык: Английский

Процитировано

158
The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma DOI Creative Commons
Lars Ny, Henrik Jespersen, Joakim Karlsson

и другие.

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Авг. 27, 2021

Abstract Preclinical studies have suggested that epigenetic therapy could enhance immunogenicity of cancer cells. We report the results PEMDAC phase 2 clinical trial ( n = 29; NCT02697630) where HDAC inhibitor entinostat was combined with PD-1 pembrolizumab in patients metastatic uveal melanoma (UM). The primary endpoint objective response rate (ORR), and met an ORR 14%. benefit at 18 weeks 28%, median progression free survival 2.1 months overall 13.4 months. Toxicities were manageable, there no treatment-related deaths. Objective responses and/or prolonged seen BAP1 wildtype tumors, one patient iris exhibited a UV signature. Longer also correlated low baseline ctDNA levels or LDH. In conclusion, inhibition anti-PD1 immunotherapy durable subset UM. Trial registration ClinicalTrials.gov number: NCT02697630 (registered 3 March 2016). EudraCT 2016–002114-50.

Язык: Английский

Процитировано

134
Advances in the clinical management of uveal melanoma DOI
Richard D. Carvajal, Joseph J. Sacco, Martine J. Jager

и другие.

Nature Reviews Clinical Oncology, Год журнала: 2023, Номер 20(2), С. 99 - 115

Опубликована: Янв. 4, 2023

Язык: Английский

Процитировано

132
Roles and mechanisms of BAP1 deubiquitinase in tumor suppression DOI Open Access
Louis Masclef, Oumaima Ahmed,

Benjamin Estavoyer

и другие.

Cell Death and Differentiation, Год журнала: 2021, Номер 28(2), С. 606 - 625

Опубликована: Янв. 18, 2021

Язык: Английский

Процитировано

116
Clinical and molecular response to tebentafusp in previously treated patients with metastatic uveal melanoma: a phase 2 trial DOI Creative Commons
Richard D. Carvajal, Marcus O. Butler, Alexander N. Shoushtari

и другие.

Nature Medicine, Год журнала: 2022, Номер 28(11), С. 2364 - 2373

Опубликована: Окт. 13, 2022

Abstract In patients with previously treated metastatic uveal melanoma, the historical 1 year overall survival rate is 37% a median of 7.8 months. We conducted multicenter, single-arm, open-label phase 2 study tebentafusp, soluble T cell receptor bispecific (gp100×CD3), in 127 treatment-refractory melanoma (NCT02570308). The primary endpoint was estimation objective response based on RECIST (Response Evaluation Criteria Solid Tumours) v1.1. Secondary objectives included safety, survival, progression-free and disease control rate. All had at least one treatment-related adverse event, rash (87%), pyrexia (80%) pruritus (67%) being most common. Toxicity mostly mild to moderate severity but greatly reduced incidence intensity after initial three doses. Despite low 5% (95% CI: 2–10%), 62% 53–70%) 16.8 months 12.9–21.3), suggesting benefit beyond traditional radiographic-based criteria. an exploratory analysis, early on-treatment reduction circulating tumour DNA strongly associated even radiographic progression. Our findings indicate that tebentafusp has promising clinical activity acceptable safety profile data ctDNA as indicator from need confirmation randomized trial.

Язык: Английский

Процитировано

93
Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma DOI
Jessica C. Hassel, Sophie Piperno‐Neumann, Piotr Rutkowski

и другие.

New England Journal of Medicine, Год журнала: 2023, Номер 389(24), С. 2256 - 2266

Опубликована: Окт. 21, 2023

Tebentafusp, a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3, is approved for adult patients who are positive HLA-A*02:01 have unresectable or metastatic uveal melanoma. The primary analysis in the present phase 3 trial supported long-term survival benefit associated with drug.

Язык: Английский

Процитировано

87
Single-cell RNA sequencing reveals intratumoral heterogeneity in primary uveal melanomas and identifies HES6 as a driver of the metastatic disease DOI Open Access

Charlotte Pandiani,

Thomas Strub, Nicolas Nottet

и другие.

Cell Death and Differentiation, Год журнала: 2021, Номер 28(6), С. 1990 - 2000

Опубликована: Янв. 18, 2021

Язык: Английский

Процитировано

80
Future perspectives of uveal melanoma blood based biomarkers DOI Creative Commons
Aaron B. Beasley, Fred K. Chen, Timothy Isaacs

и другие.

British Journal of Cancer, Год журнала: 2022, Номер 126(11), С. 1511 - 1528

Опубликована: Фев. 21, 2022

Abstract Uveal melanoma (UM) is the most common primary intraocular malignancy affecting adults. Despite successful local treatment of tumour, metastatic disease develops in up to 50% patients. Metastatic UM carries a particularly poor prognosis, with no effective therapeutic option available date. Genetic studies have demonstrated that cytogenetic features, including gene expression, somatic copy number alterations and specific mutations can allow more accurate assessment risk. Pre-emptive therapies avert metastasis are being tested clinical trials patients high-risk UM. However, current prognostic methods require an tumour biopsy, which highly invasive procedure carrying risk vision-threatening complications limited by sampling variability. Recently, new diagnostic concept known as “liquid biopsy” has emerged, heralding substantial potential for minimally genetic characterisation tumours. Here, we examine evidence supporting blood circulating cells (CTCs), DNA (ctDNA), microRNA (miRNA) exosomes biomarkers In particular, discuss these aid decision making throughout management

Язык: Английский

Процитировано

40
Uveal melanoma immunogenomics predict immunotherapy resistance and susceptibility DOI Creative Commons
Shravan Leonard‐Murali, Chetana Bhaskarla,

Ghanshyam S. Yadav

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 16, 2024

Abstract Immune checkpoint inhibition has shown success in treating metastatic cutaneous melanoma but limited efficacy against uveal melanoma, a rare variant arising from the immune privileged eye. To better understand this resistance, we comprehensively profile 100 human metastases using clinicogenomics, transcriptomics, and tumor infiltrating lymphocyte potency assessment. We find that over half of these harbor lymphocytes with potent autologous specificity, despite low mutational burden resistance to prior immunotherapies. However, observe strikingly intratumoral T cell receptor clonality within microenvironment even after harness quiescent lymphocytes, develop transcriptomic biomarker enable vivo identification ex liberation counter their growth suppression. Finally, demonstrate adoptive transfer transcriptomically selected can promote immunity patients when other immunotherapies are incapable.

Язык: Английский

Процитировано

10