Uveal melanoma: In the era of new treatments

Wespiser, M.; Neidhardt, Ève-Marie; Négrier, Sylvie

doi:10.1016/j.ctrv.2023.102599

Cited by 10 publications

(5 citation statements)

References 44 publications

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“…To treat local tumor, iodine 125 brachytherapy has been proven to have the same therapeutic effect as ophthalmologic removal 45 , 46 . Treatment for the most susceptible liver metastases includes surgical resection, chemoembolization, radioembolization, and percutaneous hepatic infusion 47 . As a clinical treatment challenge, there is no strongly recommended first-line chemotherapeutic drug for the systemic treatment of mUVM 48 .…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of a costimulatory molecule-related signature to predict the prognosis for uveal melanoma patients

Zhao,

Yu,

Song

2024

Sci Rep

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Uveal melanoma (UVM) is the most common primary tumor in adult human eyes. Costimulatory molecules (CMs) are important in maintaining T cell biological functions and regulating immune responses. To investigate the role of CMs in UVM and exploit prognostic signature by bioinformatics analysis. This study aimed to identify and validate a CMs associated signature and investigate its role in the progression and prognosis of UVM. The expression profile data of training cohort and validation cohort were downloaded from The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) dataset. 60 CM genes were identified, and 34 genes were associated with prognosis by univariate Cox regression. A prognostic signature was established with six CM genes. Further, high- and low-risk groups were divided by the median, and Kaplan–Meier (K-M) curves indicated that high-risk patients presented a poorer prognosis. We analyzed the correlation of gender, age, stage, and risk score on prognosis by univariate and multivariate regression analysis. We found that risk score was the only risk factor for prognosis. Through the integration of the tumor immune microenvironment (TIME), it was found that the high-risk group presented more immune cell infiltration and expression of immune checkpoints and obtained higher immune scores. Enrichment analysis of the biological functions of the two groups revealed that the differential parts were mainly related to cell–cell adhesion, regulation of T-cell activation, and cytokine–cytokine receptor interaction. No differences in tumor mutation burden (TMB) were found between the two groups. GNA11 and BAP1 have higher mutation frequencies in high-risk patients. Finally, based on the Genomics of Drug Sensitivity in Cancer 2 (GDSC2) dataset, drug sensitivity analysis found that high-risk patients may be potential beneficiaries of the treatment of crizotinib or temozolomide. Taken together, our CM-related prognostic signature is a reliable biomarker that may provide ideas for future treatments for the disease.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of a costimulatory molecule-related signature to predict the prognosis for uveal melanoma patients

Zhao,

Yu,

Song

2024

Sci Rep

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“…Of note, tebentafusp, an immune- -Perez et al, 2021). For a more comprehensive understanding of recent advancements in UM immunotherapy, we recommend referring to other recent reviews (Fu et al, 2022;Marseglia et al, 2021;Masaoutis et al, 2021;Wespiser et al, 2023), as our focus in this review is different.…”

Section: Comb Inations Of Immunother Apy With Targ E Ted or Epi G Ene...mentioning

confidence: 99%

“…Currently, tebentafusp has shown overall benefit in HLA-A*02:01 UM patients. Of note, new options are emerging with the use of other Bispecific T cell-engagers, Dual Affinity Re-Targeting, or CAR-T cells directed against surface proteins of UM cells during preclinical stages(Orloff et al, 2022;Wespiser et al, 2023). Promising results may be achieved by combining targeted or epigenetic agents with these novel and efficacious immunotherapy approaches, which requires clinical testing for the treatment of metastatic UM.AUTH O R CO NTR I B UTI O N SZJL, LY, and YLL directed the presentation of this review and designed the structure of this manuscript.…”

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confidence: 99%

Emerging therapeutic strategies for metastatic uveal melanoma: Targeting driver mutations

Liu,

Run‐hua,

Pan

et al. 2024

Pigment Cell Melanoma Res

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Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults. Although primary UM can be effectively controlled, a significant proportion of cases (40% or more) eventually develop distant metastases, commonly in the liver. Metastatic UM remains a lethal disease with limited treatment options. The initiation of UM is typically attributed to activating mutations in GNAQ or GNA11. The elucidation of the downstream pathways such as PKC/MAPK, PI3K/AKT/mTOR, and Hippo‐YAP have provided potential therapeutic targets. Concurrent mutations in BRCA1 associated protein 1 (BAP1) or splicing factor 3b subunit 1 (SF3B1) are considered crucial for the acquisition of malignant potential. 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.

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“…Current treatments for mUM include local surgery, radioembolization, chemoembolization, percutaneous hepatic infusion of melphalan, and systemic chemotherapy and immunotherapy. 4 However, their clinical benefit has been disappointing, although monoclonal antibodies such as anti-PD(L)1 or anti-CTLA4 have achieved encouraging efficacy in cutaneous melanoma. 4–6 Notably, recent reports have shown that a combination of nivolumab and ipilimumab can improve median overall survival over up to 12 months in patients with uveal melanoma.…”

Section: Introductionmentioning

confidence: 99%

“… 4 However, their clinical benefit has been disappointing, although monoclonal antibodies such as anti-PD(L)1 or anti-CTLA4 have achieved encouraging efficacy in cutaneous melanoma. 4–6 Notably, recent reports have shown that a combination of nivolumab and ipilimumab can improve median overall survival over up to 12 months in patients with uveal melanoma. 7 , 8 While its safety profile is concerning, as reported in two studies where over 90% patients experienced treatment-related adverse reactions, there is a medical need for more opportunities to explore novel drug with improved efficacy and higher safety profiles.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of tebentafusp in patients with metastatic uveal melanoma: A systematic review and meta-analysis

Dian,

Liu,

Zeng

et al. 2024

Human Vaccines & Immunotherapeutics

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Uveal melanoma: In the era of new treatments

Cited by 10 publications

References 44 publications

Identification and validation of a costimulatory molecule-related signature to predict the prognosis for uveal melanoma patients

Identification and validation of a costimulatory molecule-related signature to predict the prognosis for uveal melanoma patients

Emerging therapeutic strategies for metastatic uveal melanoma: Targeting driver mutations

Efficacy and safety of tebentafusp in patients with metastatic uveal melanoma: A systematic review and meta-analysis

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