Advances in the Treatment of Metastatic Uveal Melanoma

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

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 48695

Special Issue Editor


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Guest Editor
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy & Sahlgrenska University Hospital, University of Gothenburg, SE413 45 Gothenburg, Sweden
Interests: Melanoma; Immunotherapy; Checkpoint inhibition; Epigenetics; Precision medicine; Cell therapy; Clinical trials

Special Issue Information

Uveal malignant melanoma (UM) is a disease that differs biologically from cutaneous melanoma, which is reflected by a different mutation profile and a markedly lower tumor mutation burden in UM. Current treatments of the primary tumor in UM are effective using local radiotherapy or surgery. For patients developing metastatic disease, mainly engaging the liver, the situation is more challenging, with no approved drugs as of today. Recent initiatives including exploration of both local and systemic approaches are in clinical development and are using interventions in both monotherapy and in combinations. Further efforts remain to be uncovered in the clinical setting in order to improve the therapeutic outcomes for this group of patients with a high medical need.

The purpose of this issue on metastatic UM will be to offer an updated overview of the present and potentially soon new therapeutic options in metastatic UM in the clinic.

Prof. Dr. Lars Ny
Guest Editor

Manuscript Submission Information

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Keywords

  • Uveal melanoma
  • Metastasis
  • Immunotherapies
  • Checkpoint inhibitor
  • T-cell receptor
  • Epigenetics
  • Cell therapy
  • CAR-T
  • Targeted therapies
  • Chemotherapies
  • Liver directed therapy
  • Radiotherapy
  • Hepatic perfusion

Published Papers (5 papers)

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Research

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12 pages, 1153 KiB  
Article
Combination of Immune Checkpoint Inhibitors and Liver-Specific Therapies in Liver-Metastatic Uveal Melanoma: Can We Thus Overcome Its High Resistance?
by Chiara L. Blomen, Julian Kött, Tabea I. Hartung, Leopold K. Torster and Christoffer Gebhardt
Cancers 2021, 13(24), 6390; https://doi.org/10.3390/cancers13246390 - 20 Dec 2021
Cited by 10 | Viewed by 3163
Abstract
Uveal Melanoma (UM) is a rare disease; however, it is the most common primary intraocular malignant tumor in adults. Hematogenous metastasis, occurring in up to 50% of cases, mainly to the liver (90%), is associated with poor clinical course and treatment failure. In [...] Read more.
Uveal Melanoma (UM) is a rare disease; however, it is the most common primary intraocular malignant tumor in adults. Hematogenous metastasis, occurring in up to 50% of cases, mainly to the liver (90%), is associated with poor clinical course and treatment failure. In contrast to dramatic benefits of immunotherapy in many tumor entities, as seen in cutaneous melanoma, immune checkpoint inhibitors (ICI) do not achieve comparable results in Metastatic UM (MUM). The aim of this study was to investigate whether the combination of ICI with liver-directed therapies provides a potential survival benefit for those affected. This retrospective, single-center study, including n = 45 patients with MUM, compared the effect of combining ICI with liver-directed therapy (“Cohort 1”) with respect to standard therapies (“Cohort 2”) on overall survival (OS). Our results revealed a significant survival difference between Cohort 1 (median OS 22.5 months) and Cohort 2 (median OS 11.4 months), indicating that this combination may enhance the efficacy of immunotherapy and thus provide a survival benefit. There is an urgent need for randomized, prospective trials addressing the combination of liver-directed therapies and various strategies of immunotherapy (such as ICI; IMCgp100; personalized vaccines) in order to establish regimens which finally improve the prognosis of patients with MUM. Full article
(This article belongs to the Special Issue Advances in the Treatment of Metastatic Uveal Melanoma)
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Review

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27 pages, 442 KiB  
Review
Recent Advances and Challenges in Uveal Melanoma Immunotherapy
by Yihang Fu, Wei Xiao and Yuxiang Mao
Cancers 2022, 14(13), 3094; https://doi.org/10.3390/cancers14133094 - 23 Jun 2022
Cited by 23 | Viewed by 36698
Abstract
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Compared to cutaneous melanoma (CM), which mainly harbors BRAF or NRAS mutations, UM predominantly harbors GNAQ or GNA11 mutations. Although primary UM can be controlled locally, approximately 50% of patients still [...] Read more.
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Compared to cutaneous melanoma (CM), which mainly harbors BRAF or NRAS mutations, UM predominantly harbors GNAQ or GNA11 mutations. Although primary UM can be controlled locally, approximately 50% of patients still develop metastases. To date, there have been no standard therapeutic strategies for the prevention or treatment of metastases. Unfortunately, chemotherapy and targeted therapies only induce minimal responses in patients with metastatic UM, with a median survival time of only 4–5 months after metastasis detection. Immunotherapy agents, such as immune checkpoint inhibitors, have achieved pioneering outcomes in CM but have shown limited effects in UM. Researchers have explored several feasible checkpoints to identify options for future therapies. Cancer vaccines have shown little in the way of therapeutic benefit in patients with UM, and there are few ongoing trials providing favorable evidence, but adoptive cell transfer-related therapies seem promising and deserve further investigation. More recently, the immune-mobilizing monoclonal T-cell receptor against the cancer molecule tebentafusp showed impressive antitumor effects. Meanwhile, oncolytic viruses and small molecule inhibitors have also gained ground. This review highlights recent progress in burgeoning treatments and provides innovative insights on feasible strategies for the treatment of UM. Full article
(This article belongs to the Special Issue Advances in the Treatment of Metastatic Uveal Melanoma)
11 pages, 1115 KiB  
Review
TCR-Directed Therapy in the Treatment of Metastatic Uveal Melanoma
by Sophia B. Strobel, Devayani Machiraju and Jessica C. Hassel
Cancers 2022, 14(5), 1215; https://doi.org/10.3390/cancers14051215 - 26 Feb 2022
Cited by 11 | Viewed by 2994
Abstract
Metastatic uveal melanoma (mUM) is one of the most rapidly progressing tumors, with a bad prognosis and no standard-of-care treatment. Immune checkpoint inhibitors have revolutionized cancer therapy and improved overall survival in patients with metastatic cutaneous melanoma (mCM). However, this approach has been [...] Read more.
Metastatic uveal melanoma (mUM) is one of the most rapidly progressing tumors, with a bad prognosis and no standard-of-care treatment. Immune checkpoint inhibitors have revolutionized cancer therapy and improved overall survival in patients with metastatic cutaneous melanoma (mCM). However, this approach has been largely unimpressive, with no significant impact on the survival of mUM patients. Technical advances in immunotherapies have led to the development of novel T cell receptor (TCR)-based approaches to fight cancer. For the first time in over 50 years, compelling evidence demonstrates the power of TCR-based approaches for survival in mUM patients. Hence, this review summarizes novel TCR-based immunotherapeutic strategies currently in clinical studies for mUM treatment. We also discuss the potential combinational treatments to these strategies to maximize the clinical benefits. Full article
(This article belongs to the Special Issue Advances in the Treatment of Metastatic Uveal Melanoma)
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18 pages, 12621 KiB  
Review
Potential of miRNA-Based Nanotherapeutics for Uveal Melanoma
by Chun Yang, Rui Wang and Pierre Hardy
Cancers 2021, 13(20), 5192; https://doi.org/10.3390/cancers13205192 - 16 Oct 2021
Cited by 12 | Viewed by 2536
Abstract
Uveal melanoma (UM) is the most common adult intraocular cancer, and metastatic UM remains deadly and incurable. UM is a complex disease associated with the deregulation of numerous genes and redundant intracellular signaling pathways. As understanding of epigenetic dysregulation in the oncogenesis of [...] Read more.
Uveal melanoma (UM) is the most common adult intraocular cancer, and metastatic UM remains deadly and incurable. UM is a complex disease associated with the deregulation of numerous genes and redundant intracellular signaling pathways. As understanding of epigenetic dysregulation in the oncogenesis of UM has increased, the abnormal expression of microRNAs (miRNAs) has been found to be an epigenetic mechanism underlying UM tumorigenesis. A growing number of miRNAs are being found to be associated with aberrant signaling pathways in UM, and some have been investigated and functionally characterized in preclinical settings. This review summarizes the miRNAs with promising therapeutic potential for UM treatment, paying special attention to the therapeutic miRNAs (miRNA mimics or inhibitors) used to restore dysregulated miRNAs to their normal levels. However, several physical and physiological limitations associated with therapeutic miRNAs have prevented their translation to cancer therapeutics. With the advent of nanotechnology delivery systems, the development of effective targeted therapies for patients with UM has received great attention. Therefore, this review provides an overview of the use of nanotechnology drug delivery systems, particularly nanocarriers that can be loaded with therapeutic miRNAs for effective delivery into target cells. The development of miRNA-based therapeutics with nanotechnology-based delivery systems may overcome the barriers of therapeutic miRNAs, thereby enabling their translation to therapeutics, enabling more effective targeting of UM cells and consequently improving therapeutic outcomes. Full article
(This article belongs to the Special Issue Advances in the Treatment of Metastatic Uveal Melanoma)
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Other

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13 pages, 1748 KiB  
Systematic Review
Meta-Analysis of Isolated Hepatic Perfusion and Percutaneous Hepatic Perfusion as a Treatment for Uveal Melanoma Liver Metastases
by Martijn S. Bethlehem, Dimitrios Katsarelias and Roger Olofsson Bagge
Cancers 2021, 13(18), 4726; https://doi.org/10.3390/cancers13184726 - 21 Sep 2021
Cited by 14 | Viewed by 2537
Abstract
Background: Uveal melanoma is the most commonly occurring primary intraocular malignancy in adults, and patients have a high risk of developing metastatic disease, mostly in the liver. Isolated hepatic perfusion (IHP) with melphalan is a liver-directed therapy for patients with liver metastases. Percutaneous [...] Read more.
Background: Uveal melanoma is the most commonly occurring primary intraocular malignancy in adults, and patients have a high risk of developing metastatic disease, mostly in the liver. Isolated hepatic perfusion (IHP) with melphalan is a liver-directed therapy for patients with liver metastases. Percutaneous hepatic perfusion (PHP), a minimally invasive technique, is available as well. PHP benefits from the fact that the procedure can be repeated and therefore possibly offers better survival. We conducted a systematic review and meta-analysis comparing both techniques. Methods: A systematic literature search was performed using the electronic databases of Scopus, MEDLINE, Web of Science, PubMed and Cochrane CENTRAL. A total of nine articles reporting on eight studies were included in the analysis. Individual survival data were extracted from each study. Results: The median overall survival (OS) was 17.1 months for IHP and 17.3 months for PHP. The median progression-free survival (PFS) was 7.2 months for IHP and 9.6 months for PHP. The median hepatic progression-free survival was 10 months for IHP and 9.5 months for PHP. The complication rate and 30-day mortality rate were 39.1% and 5.5% for IHP and 23.8% and 1.8% for PHP. Conclusion: There was no difference in OS or PFS between IHP and PHP for patients with uveal melanoma liver metastases, but patients have significantly less of a risk for complications and mortality following PHP. Full article
(This article belongs to the Special Issue Advances in the Treatment of Metastatic Uveal Melanoma)
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