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CANCER:

Ocular Melanoma

Related cancers:
11d
Epidemiology, Diagnosis and Genetics of Retinoblastoma: ICMR Consensus Guidelines. (PubMed, Indian J Pediatr)
Histopathologic risk factors such as massive choroidal invasion and post-laminar optic nerve help in predicting the occurrence of metastasis in children with RB, while presence of microscopic residual disease requires aggressive adjuvant treatment in eyes enucleated for group E RB. The review provides a consensus document on diagnosis and genetics of RB in India.
Review • Journal
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RB1 (RB Transcriptional Corepressor 1)
13d
Sunitinib Malate or Valproic Acid in Preventing Metastasis in Patients With High-Risk Uveal Melanoma (clinicaltrials.gov)
P2, N=210, Active, not recruiting, Sidney Kimmel Cancer Center at Thomas Jefferson University | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025
Trial completion date • Trial primary completion date
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Sutent (sunitinib)
20d
Tumor DNA sampling from aqueous humor in retinoblastoma - A report from South Asia. (PubMed, Indian J Ophthalmol)
Our study supports the previous reports that AH may be used as a source of tumor-derived cfDNA. This is the first report from South Asia on isolation and genetic analysis of cfDNA from AH of RB eyes and, therefore, a big step forward in paving the role of tumor genetics in RB. Further studies are required to elucidate concordance between the tumor and AH genetic profile.
Journal
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RB1 (RB Transcriptional Corepressor 1)
28d
High-risk histopathologic features in local advanced conjunctival melanoma. (PubMed, Acta Ophthalmol)
Tumour thickness ≥ 4 mm, ulceration, the coexistence of regression and TILs, and positive BRAFV600E were risk factors for poor prognosis of CoM patients. Besides, expression level of BRAFV600E was positively correlated with the expression levels of PD-1 and PD-L1.
Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PD-1 (Programmed cell death 1)
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BRAF V600E • BRAF V600 • NRAS Q61 • NRAS Q61R • BRAF positive
29d
Pharmacogenomic Analysis of Response to Topical Tumor Necrosis Factor α Antagonist Licaminlimab (OCS-02) in Dry Eye Disease. (PubMed, Cornea)
The CC genotype of rs1800693, relatively common in patients with DED, was strongly associated with response to licaminlimab and decreased inflammatory cytokine gene expression in ocular surface cells during treatment. This study is one of the first to our knowledge to investigate pharmacogenomics in the treatment of DED.
Journal
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CXCL8 (Chemokine (C-X-C motif) ligand 8) • TNFRSF1A (TNF Receptor Superfamily Member 1A) • IL1B (Interleukin 1, beta)
30d
Emerging therapeutic strategies for metastatic uveal melanoma: Targeting driver mutations. (PubMed, Pigment Cell Melanoma Res)
Furthermore, in preclinical studies, actionable targets associated with BAP1 loss or oncogenic mutant SF3B1 have been identified, offering promising avenues for UM treatment. This review aims to summarize the emerging targeted and epigenetic therapeutic strategies for metastatic UM carrying specific driver mutations and the potential of combining these approaches with immunotherapy, with particular focus on those in upcoming or ongoing clinical trials.
Review • Journal • BRCA Biomarker • IO biomarker • Metastases
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GNAQ (G Protein Subunit Alpha Q) • SF3B1 (Splicing Factor 3b Subunit 1) • BAP1 (BRCA1 Associated Protein 1) • GNA11 (G Protein Subunit Alpha 11)
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BRCA1 mutation • GNAQ mutation • BAP1 mutation
1m
Construction of a Functional Nucleic Acid-Based Artificial Vesicle-Encapsulated Composite Nanoparticle and Its Application in Retinoblastoma-Targeted Theranostics. (PubMed, ACS Biomater Sci Eng)
Subsequently, the DNAzymes can target two different mRNAs, thereby realizing fluorescence/MR bimodal imaging and dual-gene therapy. This study is expected to provide a reliable and valuable basis for ocular tumor theranostics.
Journal
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NCL (Nucleolin)
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NCL overexpression
1m
Genetic landscape and prognosis of conjunctival melanoma in Chinese patients. (PubMed, Br J Ophthalmol)
The molecular landscape of CoM in Chinese patients was updated with new findings. A relatively high frequency of mutated FAT4 was determined in Chinese CoM patients, and decreased expression of FAT4 was found in patients with worse prognoses. In addition, both BRAF mutations and FAT4 mutations could serve as predictive factors for CoM patients.
Journal
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BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • FAT4 (FAT Atypical Cadherin 4)
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BRAF mutation • NF1 mutation • FAT4 mutation
1m
AIBI Modified Mesoporous Copper Sulfide Nanocomposites for Efficient Non-Oxygen Dependent Free Radicals-Assisted Photothermal Therapy in Uveal Melanoma. (PubMed, Small)
In vitro and in vivo experiments confirm the remarkable anti-tumor efficacy of AMPT. Notably, the study introduces an orthotopic tumor model for UM, demonstrating the feasibility of precise and effective targeted treatment within the ocular system.
Journal
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AVEN (Apoptosis And Caspase Activation Inhibitor)
1m
Autoimmune retinopathy in a patient with smoldering multiple myeloma: a case report. (PubMed, Doc Ophthalmol)
The association of autoimmune retinopathy with multiple myeloma is rare. It is crucial for physicians to be aware of such manifestations to ensure timely and appropriate diagnosis and management for patients.
Journal
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GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase)
1m
Proof of Concept of TBio-4101, Lymphodepleting Chemo, IL-2 for Relapsed/Refractory Melanoma (clinicaltrials.gov)
P1, N=25, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Jan 2024 --> Aug 2024
Trial completion date • Trial primary completion date
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BRAF (B-raf proto-oncogene) • IL2 (Interleukin 2)
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BRAF mutation • BRAF V600
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cyclophosphamide • fludarabine IV • TIDAL-01
1m
Olaparib in Combination With Pembrolizumab for Advanced Uveal Melanoma (clinicaltrials.gov)
P2, N=37, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2027 --> Dec 2025
Trial completion date • Combination therapy • Metastases
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Keytruda (pembrolizumab) • Lynparza (olaparib)
1m
Study in Subjects With Small Primary Choroidal Melanoma (clinicaltrials.gov)
P1/2, N=57, Completed, Aura Biosciences | Phase classification: P1b/2 --> P1/2
Phase classification
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belzupacap sarotalocan (AU-011)
1m
ATOM: Adjuvant Tebentafusp in High Risk Ocular Melanoma (clinicaltrials.gov)
P3, N=290, Not yet recruiting, European Organisation for Research and Treatment of Cancer - EORTC
New P3 trial • Metastases
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Kimmtrak (tebentafusp-tebn)
1m
Melanoma Arising Beneath the Lateral Rectus Muscle in a Teenager With Ocular Melanocytosis: Possible Origin From Intrascleral Melanocytes. (PubMed, Ophthalmic Plast Reconstr Surg)
The histopathology and molecular genetics designated the lesion as having a uveal melanoma-like profile, suggesting that it may behave as a choroidal melanoma. This case underscores the importance of the association between ocular melanocytosis and orbital melanoma and provides additional evidence for primary orbital melanoma etiopathogenesis.
Journal
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NF1 (Neurofibromin 1) • GNAQ (G Protein Subunit Alpha Q)
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NF1 mutation
2ms
Retinoblastoma vulnerability to combined de novo and salvage pyrimidine ribonucleotide synthesis pharmacologic blockage. (PubMed, Heliyon)
Furthermore, these genome alterations associate with malignancy. These results indicate that targeting pyrimidine ribonucleotide synthesis may be an effective therapeutic strategy to consider as a treatment for retinoblastoma.
Journal
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DHODH (Dihydroorotate Dehydrogenase (Quinone))
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TP53 mutation
2ms
When the second comes first- rhabdomyosarcoma preceding heritable retinoblastoma- a case report. (PubMed, BMC Ophthalmol)
Non-ocular SPTs like sarcomas are usually known to manifest in heritable rb survivors with a lag of two to three decades (earlier if exposure to radiation is present) from the presentation of the rb. However, in our case, this seemed to be reversed with the RMS being manifest at an unusual early age and the rb being diagnosed at a later point in time.
Journal
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RB1 (RB Transcriptional Corepressor 1)
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RB1 mutation
2ms
Uveal melanoma: Recent advances in immunotherapy. (PubMed, World J Clin Oncol)
As a result, more effective immunotherapeutic approaches, such as cancer vaccines, adoptive cell transfer, and other new molecules are currently being studied. In this review, we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.
Review • Journal • IO biomarker
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BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • GNAQ (G Protein Subunit Alpha Q) • GNA11 (G Protein Subunit Alpha 11)
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BRAF mutation • NRAS mutation • GNAQ mutation
2ms
Prox1 Suppresses Proliferation and Drug Resistance of Retinoblastoma Cells via Targeting Notch1. (PubMed, Curr Med Sci)
These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1, implying that Prox1 could be a potential therapeutic target for RB.
Journal
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NOTCH1 (Notch 1)
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NOTCH1 expression • NOTCH1 overexpression
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vincristine
2ms
Trial completion date • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • PGR (Progesterone receptor)
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ER positive • HR positive • BRAF mutation • HER-2 negative • PTEN mutation + HR positive
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Opdivo (nivolumab) • Hiltonol (poly-ICLC) • PNV21 vaccine
2ms
Targeted Therapy and Immunotherapy for Advanced Malignant Conjunctival Tumors: Systematic Review. (PubMed, Ophthalmic Plast Reconstr Surg)
Despite limited clinical case reports and short-term follow-ups, targeted therapy and immunotherapy have shown promising results for advanced malignant conjunctival tumors.
Review • Journal • Metastases
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene)
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Rituxan (rituximab)
2ms
Ziv-aflibercept plus pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment. (PubMed, Cancer Immunol Immunother)
Although limited by sample size and follow-up, these findings highlight the potential of the combination of ziv-aflibercept antiangiogenic therapy with pembrolizumab in patients with advanced melanoma resistant to anti-PD-1 treatment and the need for further research to improve outcomes in anti-PD-1-resistant melanoma.
Journal • Metastases
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PD-L1 (Programmed death ligand 1) • CXCL10 (Chemokine (C-X-C motif) ligand 10)
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Keytruda (pembrolizumab) • Zaltrap (ziv-aflibercept IV)
3ms
Natural killer cells drive 4-1BBL positive uveal melanoma towards EMT and metastatic disease. (PubMed, J Exp Clin Cancer Res)
Taken together, the present study demonstrates a role of NK cells in the aggravation of uveal melanoma towards metastatic disease.
Journal • Metastases
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BAP1 (BRCA1 Associated Protein 1) • TNFA (Tumor Necrosis Factor-Alpha) • CD73 (5'-Nucleotidase Ecto) • NT5E (5'-Nucleotidase Ecto) • ZEB1 (Zinc Finger E-box Binding Homeobox 1)
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BAP1 mutation • CD73 expression • ZEB1 expression
3ms
Superb Microvascular Intraocular Tumor Imaging Study (SMITIS) (clinicaltrials.gov)
P=N/A, N=20, Active, not recruiting, Centre Hospitalier Universitaire de Nice | Not yet recruiting --> Active, not recruiting | Trial completion date: Sep 2022 --> Sep 2024 | Trial primary completion date: Sep 2022 --> Apr 2023
Enrollment closed • Trial completion date • Trial primary completion date
3ms
Ultrasound-enhanced nano catalyst with ferroptosis-apoptosis combined anticancer strategy for metastatic uveal melanoma. (PubMed, Biomaterials)
The FeP NPs were assembling by stimulating gallic acid-Fe (III) and paclitaxel, then could be internalized into tumor cells under the cooperative effect of ultrasound, which further activates the intracellular Fenton reaction and generates high reactive oxygen species levels, ultimately leading to mitochondrial damage, lipid per-oxidation, and apoptosis...More importantly, the level of the promoting-metastatic factor nerve growth factor receptor (NGFR) secreted by cancer cells is significantly reduced, further limits cancer metastasis to the cervical lymph node and finally inhibits lung metastasis of uveal melanoma. We believe that these designed ultrasound-enhanced nanoparticles possess potential clinical application for preventing the regeneration and metastasis of uveal melanoma.
Journal • Metastases
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NGFR (Nerve Growth Factor Receptor)
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paclitaxel
3ms
Single-cell transcriptomics enable the characterization of local extension in retinoblastoma. (PubMed, Commun Biol)
These results suggest that SOX4 might drive RB local extension. Our study presents a single-cell transcriptomic landscape of intraocular and extraocular RB samples, improving our understanding of RB local extension at the single-cell resolution and providing potential therapeutic targets for RB patients.
Journal
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SOX4 (SRY-Box Transcription Factor 4)
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Chr amplification(6p)
3ms
NADOM: Neoadjuvant/Adjuvant Trial of Darovasertib in Ocular Melanoma (clinicaltrials.gov)
P2, N=15, Active, not recruiting, Anthony Joshua, FRACP | Recruiting --> Active, not recruiting | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2023 --> Nov 2024
Enrollment closed • Trial completion date • Trial primary completion date
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darovasertib (IDE196)
3ms
PD-L1 is a biomarker of real-world clinical outcomes for anti-CTLA-4 plus anti-PD-1 or anti-PD-1 monotherapy in metastatic melanoma. (PubMed, Eur J Cancer)
Our findings support previous exploratory analyses of Checkmate-067, highlighting that improved clinical outcomes with combination therapy are not established in unselected patients with high (≥1%) tumor PD-L1 expression.
Clinical data • Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world • Metastases
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PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene)
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PD-L1 expression • BRAF wild-type
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Opdivo (nivolumab) • Yervoy (ipilimumab)
3ms
Enrollment closed
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Melblez Kit (melphalan hepatic delivery system)
3ms
FOCUS: Percutaneous Hepatic Perfusion in Patients With Hepatic-dominant Ocular Melanoma (clinicaltrials.gov)
P3, N=102, Completed, Delcath Systems Inc. | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Aug 2023
Trial completion • Trial completion date
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Melblez Kit (melphalan hepatic delivery system)
3ms
Uveal melanoma modeling in mice and zebrafish. (PubMed, Biochim Biophys Acta Rev Cancer)
Here, we provide an overview of the molecular mechanisms and pharmacological studies using mouse and zebrafish UM models. Finally, we highlight promising therapeutics and discuss future considerations using UM models such as optimal inoculation sites, use of BAP1-cell lines and the rise of zebrafish models.
Preclinical • Review • Journal
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BAP1 (BRCA1 Associated Protein 1)
3ms
Hepatic Ablation of Melanoma Metastases to Enhance Immunotherapy Response, a Phase I Clinical Trial (HAMMER I) (clinicaltrials.gov)
P1, N=18, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Mar 2025 --> Jun 2025 | Trial primary completion date: Mar 2024 --> Jun 2024
Trial completion date • Trial primary completion date
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IFNA1 (Interferon Alpha 1)
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Opdivo (nivolumab) • Yervoy (ipilimumab)
3ms
Combined Osteopontin Blockade and Type 2 Classical Dendritic Cell Vaccination as Effective Synergetic Therapy for Conjunctival Melanoma. (PubMed, J Immunol)
Moreover, tumor progression, monocyte-derived DC infiltration, and intratumoral angiogenesis were significantly reduced, whereas survival and CD8+ T cell infiltration were increased in treated mice compared with the control group. Therefore, we identified OPN blockade in combination with cDC2 vaccination as a potential future therapeutic intervention for early stages of CM by combining antiangiogenic and host immune stimulating effects.
Journal
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CD8 (cluster of differentiation 8) • SPP1 (Secreted Phosphoprotein 1) • ITGAE (Integrin Subunit Alpha E) • CDK1 (Cyclin-dependent kinase 1)
4ms
A Review of the Utility of Intra-Arterial Chemotherapy in the Treatment of Retinoblastoma (SIR 2024)
The introduction of intra-arterial chemotherapy has provided a safe, effective, and minimally invasive alternative to systemic chemotherapy that can both minimize chemotherapy side effects and avoid enucleation. Further prospective studies can better characterize IAC's benefits and limitations relative to more established treatment modalities.
Review
|
RB1 (RB Transcriptional Corepressor 1)
4ms
PEMDAC: Efficacy Study of Pembrolizumab With Entinostat to Treat Metastatic Melanoma of the Eye (clinicaltrials.gov)
P2, N=29, Completed, Vastra Gotaland Region | Active, not recruiting --> Completed | Trial completion date: Aug 2023 --> Jan 2023 | Trial primary completion date: Aug 2021 --> Jan 2023
Trial completion • Trial completion date • Trial primary completion date
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Keytruda (pembrolizumab) • Jingzhuda (entinostat)
4ms
Aqueous Humor Liquid Biopsy as a Companion Diagnostic for Retinoblastoma: implications for diagnosis, prognosis and therapeutic options. Five years of Progress. (PubMed, Am J Ophthalmol)
Establishing an AH liquid biopsy for RB is aimed at addressing 1) our inability to biopsy tumor tissue and 2) the lack of molecular biomarkers for intraocular prognosis. Current management decisions for RB are made based solely on clinical features without objective molecular testing. This prognostic study shows great promise for using AH as a companion diagnostic.
Journal • Liquid biopsy • Companion diagnostic • Biopsy
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RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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RB1 deletion • RB deletion
4ms
Characterisation of the protein expression of the emerging immunotherapy targets VISTA, LAG-3 and PRAME in primary uveal melanoma: insights from a southern French patient cohort. (PubMed, Pathology)
PRAME nuclear positivity in melanoma cells was associated with epithelioid cell dominant (>90%) UM histological subtype, higher mitotic numbers and a higher percentage of chromosome 8q gain. This study proposes VISTA as a novel relevant immune checkpoint molecule in primary UM and contributes to confirm LAG-3 and PRAME as potentially important immunotherapy targets in the treatment of UM patients, helping to expand the number of immunotherapy candidate molecules that are relevant to modulate in this aggressive cancer.
Journal • IO biomarker
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CD8 (cluster of differentiation 8) • BAP1 (BRCA1 Associated Protein 1) • LAG3 (Lymphocyte Activating 3) • PRAME (Preferentially Expressed Antigen In Melanoma) • VSIR (V-Set Immunoregulatory Receptor)
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CD8 positive • LAG3 expression • PRAME expression
4ms
Detection of the Uveal Melanoma-Associated Mutation GNAQ Q209P from Liquid Biopsy Using CRISPR/Cas12a Technology. (PubMed, Anal Chem)
Coupled with allele-specific PCR, it constitutes a sensitive platform for liquid biopsy detection, capable of sensing GNAQ Q209P in plasma samples with a low ctDNA concentration and fractional abundance. Finally, our method was validated using plasma samples from metastatic UM patients.
Journal • Liquid biopsy • Biopsy
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GNAQ (G Protein Subunit Alpha Q)
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GNAQ mutation • GNAQ Q209P
4ms
Multi-omics approaches identify novel prognostic biomarkers of autophagy in uveal melanoma. (PubMed, J Cancer Res Clin Oncol)
We identified six novel potential prognostic biomarkers in UVM, all of which are associated with autophagy and TME. These findings will shed new light on UVM therapy with inhibitors targeting these biomarkers expected to regulate autophagy and reshape the TME, significantly improving UVM treatment outcomes.
Journal
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SPHK1 (Sphingosine Kinase 1) • HTR2B (5-Hydroxytryptamine Receptor 2B)
5ms
A multicenter study validates the WHO 2022 classification for conjunctival melanocytic intraepithelial lesions with clinical and prognostic relevance. (PubMed, Lab Invest)
Invasive melanoma only occurred in 47% cases that were assessed as high-grade C-MIL. This extensive international collaborative study is the first to undertake a comprehensive review of the WHO-EYE05 C-MIL scoring system, which showed good interobserver agreement and reproducibility.
Clinical • Journal
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SOX10 (SRY-Box 10) • PRAME (Preferentially Expressed Antigen In Melanoma) • MLANA (Melan-A)
5ms
Advanced Technologies of Drug Delivery to the Posterior Eye Segment Targeting Angiogenesis and Ocular Cancer. (PubMed, Crit Rev Ther Drug Carrier Syst)
Adopting a non-invasive or minimally invasive approach for delivery of anti-VEGF agents would not only address the bioavailability issues but also improve patient adherence to therapy overcoming the side effects associated with invasive approach. The present review focuses on the eye cancer, angiogenesis and various novel ocular drug delivery systems that can facilitate inhibition of VEGF in the posterior eye segment by overcoming the eye barriers.
Journal • Metastases
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RB1 (RB Transcriptional Corepressor 1)
5ms
Direct early growth response-1 knockdown decreases melanoma viability independent of mitogen-activated extracellular signal-related kinase inhibition. (PubMed, Melanoma Res)
Treatment with MEK inhibitor (trametinib) was then assessed in two cutaneous (MEL888, MEL624) and one conjunctival (YUARGE 13-3064) melanoma cell line...In a malignant melanoma cell population, MEK inhibition reduced viability in both cutaneous and conjunctival melanoma with a profound downstream reduction in EGR1 expression. Targeted knockdown of EGR1 reduced both cutaneous and conjunctival melanoma cell viability independent of MEK inhibition, suggesting a key role for EGR1 in melanoma pathobiology.
Journal
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EGR1 (Early Growth Response 1)
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Mekinist (trametinib)