Uveal Melanoma: A Review of the Literature

Singh, Manni; Durairaj, Priya; Yeung, Jensen

doi:10.1007/s40487-018-0056-8

Cited by 51 publications

(44 citation statements)

References 132 publications

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“…Despite a good control of the localised tumour by radiotherapy or surgery, up to 50% of UM patients develop metastases mainly in the liver. Once the disease has spread, the prognosis is poor with median survival of 9 months, and the treatment is challenging with absence of efficient therapeutic strategies [2,3].…”

Section: Introductionmentioning

confidence: 99%

Preclinical evaluation of drug combinations identifies co-inhibition of Bcl-2/XL/W and MDM2 as a potential therapy in uveal melanoma

Decaudin

Leitz

Némati

et al. 2020

European Journal of Cancer

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Introduction: Uveal melanoma (UM) is a rare and malignant intraocular tumour with a dismal prognosis. Despite a good control of the primary tumour by radiation or surgery, up to 50% of patients subsequently develop metastasis for which no efficient treatment is yet available. Methodology: To identify therapeutic opportunities, we performed an in vitro screen of 30 combinations of different inhibitors of pathways that are dysregulated in UM. Effects of drug combinations on viability, cell cycle and apoptosis were assessed in eight UM cell lines. The best synergistic combinations were further evaluated in six UM patient-derived xenografts (PDXs). Results: We demonstrated that the Bcl-2/X L /W inhibitor (ABT263) sensitised the UM cell lines to other inhibitors, mainly to mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase (MEK) and murine double minute 2 (MDM2) inhibitors. mTOR (RAD001) and MEK1/2 (trametinib) inhibitors were efficient as single agents, but their combinations with ABT263 displayed no synergism in UM PDXs. In contrast, the combination of

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Section: Introductionmentioning

confidence: 99%

Preclinical evaluation of drug combinations identifies co-inhibition of Bcl-2/XL/W and MDM2 as a potential therapy in uveal melanoma

Decaudin

Leitz

Némati

et al. 2020

European Journal of Cancer

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“…At present, no effective treatment exists to prevent metastasis, but early detection and intervention could be critical for a positive long-term survival outcome in UM. 143 , 144 Metastatic UM responds poorly to chemotherapy, targeted therapy, and immunotherapy. Nevertheless, unlike cutaneous melanoma, UM metastases generally do not respond to immune-checkpoint inhibitors.…”

Section: Therapeutic Optionsmentioning

confidence: 99%

Uveal melanoma: progress in molecular biology and therapeutics

Shi

Yang

et al. 2020

Ther Adv Med Oncol

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Uveal melanoma (UM) is the most common intraocular malignancy in adults. So far, no systemic therapy or standard treatment exists to reduce the risk of metastasis and improve overall survival of patients. With the increased knowledge regarding the molecular pathways that underlie the oncogenesis of UM, it is expected that novel therapeutic approaches will be available to conquer this disease. This review provides a summary of the current knowledge of, and progress made in understanding, the pathogenesis, genetic mutations, epigenetics, and immunology of UM. With the advent of the omics era, multi-dimensional big data are publicly available, providing an innovation platform to develop effective targeted and personalized therapeutics for UM patients. Indeed, recently, a great number of therapies have been reported specifically for UM caused by oncogenic mutations, as well as other etiologies. In this review, special attention is directed to advancements in targeted therapies. In particular, we discuss the possibilities of targeting: GNAQ/GNA11, PLCβ, and CYSLTR2 mutants; regulators of G-protein signaling; the secondary messenger adenosine diphosphate (ADP)-ribosylation factor 6 (ARF6); downstream pathways, such as those involving mitogen-activated protein kinase/MEK/extracellular signal-related kinase, protein kinase C (PKC), phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (mTOR), Trio/Rho/Rac/Yes-associated protein, and inactivated BAP1; and immune-checkpoint proteins cytotoxic T-lymphocyte antigen 4 and programmed cell-death protein 1/programmed cell-death ligand 1. Furthermore, we conducted a survey of completed and ongoing clinical trials applying targeted and immune therapies for UM. Although drug combination therapy based on the signaling pathways involved in UM has made great progress, targeted therapy is still an unmet medical need.

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“…These latter have an elective tropism for the hepatic parenchyma, so that the liver represents the primary site of metastatization in more than 90% of cases and about 50% of these patients have purely liver metastases [ 59 – 61 ]. Without any therapy, the median overall survival of patients affected by uveal melanoma with hepatic metastases is < 6 months [ 62 ]. Therefore, the therapeutic management of liver metastases from uveal melanoma represents, even today, an unresolved issue.…”

Section: Post Treatment Follow-upmentioning

confidence: 99%

Diagnostic methods and therapeutic options of uveal melanoma with emphasis on MR imaging—Part II: treatment indications and complications

Foti¹,

Travali²,

Farina³

et al. 2021

Insights Imaging

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Therapy of uveal melanoma aims to preserve the eye and its function and to avoid metastatic dissemination. The treatment choice is difficult and must keep into account several factors; the therapeutic strategy of uveal melanoma should therefore be personalized, sometimes requiring to combine different treatment techniques. Nowadays globe-sparing radiotherapy techniques are often preferred to enucleation. Plaque brachytherapy, the most commonly used eye-preserving therapy, is suitable for small- and medium-sized uveal melanomas. Proton beam radiotherapy is indicated for tumours with noticeable size, challenging shape and location, but is more expensive and less available than brachytherapy. Enucleation is currently restricted to advanced tumours, uveal melanomas with orbital or optic nerve involvement, blind and painful eyes because of treatment-related complications (neovascular glaucoma, chronic inflammatory processes). The effect of proton beam therapy on neoplastic tissue is related to direct cytotoxic action of the radiations, impairment of neoplastic vascular supply and immunologic response. Complications after radiotherapy are frequent and numerous and mainly related to tumour thickness, radiation dose and distance between the tumour and optic nerve. The purpose of this pictorial review is to provide the radiologists with awareness about diagnostic methods and therapeutic options of uveal melanoma. In the present second section, we discuss the therapeutic management of uveal melanoma, describing the main ocular-conserving radiotherapic techniques. We subsequently present an overview of the effects of radiations on neoplastic tissue. Lastly, we review ocular complications following radiotherapy that should be evaluated by radiologists during follow-up MRI examinations.

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Uveal Melanoma: A Review of the Literature

Cited by 51 publications

References 132 publications

Preclinical evaluation of drug combinations identifies co-inhibition of Bcl-2/XL/W and MDM2 as a potential therapy in uveal melanoma

Preclinical evaluation of drug combinations identifies co-inhibition of Bcl-2/XL/W and MDM2 as a potential therapy in uveal melanoma

Uveal melanoma: progress in molecular biology and therapeutics

Diagnostic methods and therapeutic options of uveal melanoma with emphasis on MR imaging—Part II: treatment indications and complications

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