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Special Issue "Therapies of Uveal Melanoma"

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (30 May 2023) | Viewed by 7140

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Special Issue Editors

Dr. Manuel Rodrigues
E-Mail Website
Guest Editor

Department of Medical Oncology, Institut Curie, Paris Science & Lettres Research University, 75005 Paris, France
Institut Curie, Institut national de la santé et de la recherche médicale (INSERM), PSL Research University, U830, 75005 Paris, France
Interests: gynecological and ocular cancer

Dr. Sergio Roman-Roman

E-Mail Website
Guest Editor

Translational Research Department, Institut Curie, Paris, France
Interests: antitumor; uveal melanoma; tumor models

Special Issue Information

Dear Colleagues,

Uveal melanoma (UM) is the most common intraocular malignant tumor in adults. Primary tumors are treated with conservative strategies, such as brachytherapy or proton-beam therapy but sometimes require enucleation. Even if local treatment is very efficient, up to 50% of patients will eventually suffer metastatic recurrence. Risk of metastatic recurrence can be estimated with TNM staging, as well as transcriptomic or genomic signatures. When metastatic, UM is associated with poor prognosis. Until recently with the positive results of two clinical trials with tebentafusp, no treatment had previously shown clinical efficiency on metastatic UMs. Various inhibitors have been tested in clinical trials to target GNAQ/GNA11-activating mutations, including MAPK and PKC, with limited, if any, clinical benefit. Cytotoxic drugs and immune checkpoint inhibitors are associated with limited activity, although some exceptional responder patients have been reported.

This Special Issue will focus on the treatment of primary, as well as metastatic, UM patients. We will not only accept papers on the different, current and future therapeutic options, but also on the development of new targets and new models, as well as on the supportive and psychological care of our patients.

Examples of eligible themes:
Diagnosis and Prognosis
Ophthalmology
Pathology including Molecular Pathology
Prognostication and psychological consequences
Patient advocacy
Local treatment approaches
Surgery
Radiotherapy / Protontherapy
Consequences including radio-induced retinopathies and psychological consequences
Follow-up of UM patients after local treatment
Imaging
Circulating biomarkers
Treatment of metastatic disease
Surgery
Liver-directed therapies including chemoembolization
Radiotherapy
Chemotherapy
Immunotherapy
Targeted therapies
Supportive care including palliative and psychological care

Best regards,

Dr. Manuel Rodrigues
Dr. Sergio Roman-Roman
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Uveal melanoma (UM)
Ophthalmology
Pathology
Surgery
Diagnosis and prognosis
Psychological consequences
Local treatment approaches
Treatment of metastatic disease
Immunotherapy
Supportive care

Published Papers (4 papers)

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Research

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Open AccessArticle

FAK Inhibitor-Based Combinations with MEK or PKC Inhibitors Trigger Synergistic Antitumor Effects in Uveal Melanoma

Sophie Piperno-Neumann

and

Cancers 2023, 15(8), 2280; https://doi.org/10.3390/cancers15082280 - 13 Apr 2023

Viewed by 1211

Abstract

Uveal Melanoma (UM) is a rare and malignant intraocular tumor with dismal prognosis. Even if radiation or surgery permit an efficient control of the primary tumor, up to 50% of patients subsequently develop metastases, mainly in the liver. The treatment of UM metastases is challenging and the patient survival is very poor. The most recurrent event in UM is the activation of Gαq signaling induced by mutations in GNAQ/11. These mutations activate downstream effectors including protein kinase C (PKC) and mitogen-activated protein kinases (MAPK). Clinical trials with inhibitors of these targets have not demonstrated a survival benefit for patients with UM metastasis. Recently, it has been shown that GNAQ promotes YAP activation through the focal adhesion kinase (FAK). Pharmacological inhibition of MEK and FAK showed remarkable synergistic growth-inhibitory effects in UM both in vitro and in vivo. In this study, we have evaluated the synergy of the FAK inhibitor with a series of inhibitors targeting recognized UM deregulated pathways in a panel of cell lines. The combined inhibition of FAK and MEK or PKC had highly synergistic effects by reducing cell viability and inducing apoptosis. Furthermore, we demonstrated that these combinations exert a remarkable in vivo activity in UM patient-derived xenografts. Our study confirms the previously described synergy of the dual inhibition of FAK and MEK and identifies a novel combination of drugs (FAK and PKC inhibitors) as a promising strategy for therapeutic intervention in metastatic UM. Full article

(This article belongs to the Special Issue Therapies of Uveal Melanoma)

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Open AccessArticle

Cerivastatin Synergizes with Trametinib and Enhances Its Efficacy in the Therapy of Uveal Melanoma

and

Cancers 2023, 15(3), 886; https://doi.org/10.3390/cancers15030886 - 31 Jan 2023

Viewed by 1077

Abstract

Background: Metastatic uveal melanoma (MUM) is a highly aggressive, therapy-resistant disease. Driver mutations in Gα-proteins GNAQ and GNA11 activate MAP-kinase and YAP/TAZ pathways of oncogenic signalling. MAP-kinase and MEK-inhibitors do not significantly block MUM progression, likely due to persisting YAP/TAZ signalling. Statins inhibit YAP/TAZ activation by blocking the mevalonate pathway, geranyl-geranylation, and subcellular localisation of the Rho-GTPase. We investigated drugs that affect the YAP/TAZ pathway, valproic acid, verteporfin and statins, in combination with MEK-inhibitor trametinib. Methods: We established IC50 values of the individual drugs and monitored the effects of their combinations in terms of proliferation. We selected trametinib and cerivastatin for evaluation of cell cycle and apoptosis. Synergism was detected using isobologram and Chou–Talalay analyses. The most synergistic combination was tested in vivo. Results: Synergistic concentrations of trametinib and cerivastatin induced a massive arrest of proliferation and cell cycle and enhanced apoptosis, particularly in the monosomic, BAP1-mutated UPMM3 cell line. The combined treatment reduced ERK and AKT phosphorylation, increased the inactive, cytoplasmatic form of YAP and significantly impaired the growth of UM cells with monosomy of chromosome 3 in NSG mice. Conclusion: Statins can potentiate the efficacy of MEK inhibitors in the therapy of UM. Full article

(This article belongs to the Special Issue Therapies of Uveal Melanoma)

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Review

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Open AccessReview

Ocular Complications of Radiotherapy in Uveal Melanoma

Mihail Zemba

Otilia-Maria Dumitrescu

Alina Gabriela Gheorghe

Madalina Radu

Mihai Alexandru Ionescu

Andrei Vatafu

and

Valentin Dinu

Cancers 2023, 15(2), 333; https://doi.org/10.3390/cancers15020333 - 04 Jan 2023

Cited by 4 | Viewed by 1368

Abstract

Uveal melanoma is the most common primary malignant intraocular tumor in adults. Radiation therapy has replaced enucleation and is now the preferred treatment in most cases. Nonetheless, around 70% of patients develop radiation-related complications, some of which are vision-threatening. The objective of this review is to present the most important complications associated with radiotherapy in the treatment of uveal melanoma and their pathogenesis, incidence, risk factors, and available preventive and therapeutic measures. The most common complications are cataracts, with a reported incidence ranging from 4% to 69%, and radiation retinopathy, reported in 5–68% of cases. Radiation-related complications are responsible for approximately half of secondary enucleations, the leading cause being neovascular glaucoma. A poor visual outcome is mainly associated with the presence of radiation retinopathy and radiation optic neuropathy. Therapeutic options are available for the majority of complications with the notable exception of optic neuropathy. However, many studies report a final visual acuity of less than 20/200 in more than 60% of treated eyes. Reducing complication rates can be achieved by lowering the dose of radiation, with the use of eccentric, customized plaques and careful planning of the irradiation delivery in order to protect structures vital to vision and by associating radiation therapy with other methods with the aim of reducing tumor volume. Full article

(This article belongs to the Special Issue Therapies of Uveal Melanoma)

Open AccessReview

New Perspectives for Eye-Sparing Treatment Strategies in Primary Uveal Melanoma

and

Cancers 2022, 14(1), 134; https://doi.org/10.3390/cancers14010134 - 28 Dec 2021

Cited by 6 | Viewed by 2673

Abstract

Uveal melanoma is the most common intraocular malignancy and arises from melanocytes in the choroid, ciliary body, or iris. The current eye-sparing treatment options include surgical treatment, plaque brachytherapy, proton beam radiotherapy, stereotactic photon radiotherapy, or photodynamic therapy. However, the efficacy of these methods is still unsatisfactory. This article reviews several possible new treatment options and their potential advantages in treating localized uveal melanoma. These methods may be based on the physical destruction of the cancerous cells by applying ultrasounds. Two examples of such an approach are High-Intensity Focused Ultrasound (HIFU)—a promising technology of thermal destruction of solid tumors located deep under the skin and sonodynamic therapy (SDT) that induces reactive oxygen species. Another approach may be based on improving the penetration of anti-cancer agents into UM cells. The most promising technologies from this group are based on enhancing drug delivery by applying electric current. One such approach is called transcorneal iontophoresis and has already been shown to increase the local concentration of several different therapeutics. Another technique, electrically enhanced chemotherapy, may promote drug delivery from the intercellular space to cells. Finally, new advanced nanoparticles are developed to combine diagnostic imaging and therapy (i.e., theranostics). However, these methods are mostly at an early stage of development. More advanced and targeted preclinical studies and clinical trials would be needed to introduce some of these techniques to routine clinical practice. Full article

(This article belongs to the Special Issue Therapies of Uveal Melanoma)

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Special Issue "Therapies of Uveal Melanoma"

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