Article
Oncology
Sandra Garcia-Mulero, Roberto Fornelino, Marco Punta, Stefano Lise, Mar Varela, Luis P. del Carpio, Rafael Moreno, Marcel Costa-Garcia, Dietmar Rieder, Zlatko Trajanoski, Alena Gros, Ramon Alemany, Josep Maria Piulats, Rebeca Sanz-Pamplona
Summary: Uveal melanoma (UM), the most common ocular malignancy in adults, is associated with mutations in the GNAQ and GNA11 genes. This study found that these mutations may be recognized by the immune system and samples carrying the Q209L mutation showed a higher immune-reactive phenotype. Regarding cancer risk, HLA genotypes with low Q209L affinity were more frequent in UM patients compared to the general population.
Review
Oncology
Paula Silva-Rodriguez, Daniel Fernandez-Diaz, Manuel Bande, Maria Pardo, Lourdes Loidi, Maria Jose Blanco-Teijeiro
Summary: Uveal melanoma is a complex disease with various genetic mutations, and GNAQ and GNA11 genes play a crucial role in its development and progression. The mutations in these genes activate important signaling pathways and have been suggested as potential therapeutic targets.
Article
Cell Biology
Vickie Y. Jo, Eleanor Russell-Goldman, Charles H. Yoon, Leona A. Doyle, John Hanna
Summary: Melanoma arising in extracutaneous blue naevus has molecular similarities to melanoma arising in cutaneous blue naevus and uveal melanoma, supporting the concept of melanoma originating from extracutaneous blue naevus and indicating common pathogenic mechanisms. This finding also highlights the distinction between these melanomas and conventional UV-associated melanoma. These findings have significant implications for prognosis and therapy.
Article
Biochemistry & Molecular Biology
Yongyun Li, Jie Yang, Qianqian Zhang, Shiqiong Xu, Wei Sun, Shengfang Ge, Xiaowei Xu, Martine J. Jager, Renbing Jia, Jianming Zhang, Xianqun Fan
Summary: This study reports the discovery of a new inhibitor, elesclomol, for uveal melanoma by transporting copper ions into mitochondria and generating reactive oxygen species in GNAQ/11-mutant cells, which inhibits cell migration and tumor growth.
Article
Oncology
Claudia H. D. Le Guin, Norbert Bornfeld, Nikolaos E. Bechrakis, Leyla Jabbarli, Heike Richly, Dietmar R. Lohmann, Michael Zeschnigk
Summary: The study found that detecting ctDNA signals in the plasma of patients with uveal melanoma could provide a time advantage over clinical diagnosis of metastases or tumor recurrence, and longer lead times are expected with shortened intervals between samplings.
Article
Oncology
S. Piperno-Neumann, M. S. Carlino, V. Boni, D. Loirat, F. M. Speetjens, J. J. Park, E. Calvo, R. D. Carvajal, M. Nyakas, J. Gonzalez-Maffe, X. Zhu, M. D. Shirley, T. Ramkumar, A. Fessehatsion, H. E. Burks, P. Yerramilli-Rao, E. Kapiteijn
Summary: This study evaluated the safety and efficacy of LXS196, an oral protein kinase C inhibitor, in patients with uveal melanoma. The results showed manageable toxicity and encouraging clinical activity of LXS196 in these patients.
BRITISH JOURNAL OF CANCER
(2023)
Article
Biotechnology & Applied Microbiology
Sathya Neelature Sriramareddy, Fernanda Faiao-Flores, Michael F. Emmons, Biswarup Saha, Srikumar Chellappan, Clayton Wyatt, Inna Smalley, Jonathan D. Licht, Michael A. Durante, J. William Harbour, Keiran S. M. Smalley
Summary: This study investigates the role of HDAC11 in uveal melanoma and finds that it plays a crucial role in therapy adaptation by modulating the YAP/TAZ signaling pathway, leading to the escape of MEKi therapy.
CANCER GENE THERAPY
(2022)
Review
Oncology
M. Wespiser, E. Neidhardt, S. Negrier
Summary: Uveal melanoma is the leading intraocular tumor worldwide, predominantly affecting Caucasian populations. Recent advancements in conservative and radioactive treatments have improved outcomes for localized tumors. However, despite optimal management, half of the patients develop metastatic disease with liver involvement in 90% of cases. This review provides an overview of therapeutic options, including new immunomodulatory treatments and targeted therapies, for localized or metastatic UM disease.
CANCER TREATMENT REVIEWS
(2023)
Article
Oncology
Anna Han, Dzmitry Mukha, Vivian Chua, Timothy J. Purwin, Manoela Tiago, Bhavik Modasia, Usman Baqai, Jenna L. Aumiller, Nelisa Bechtel, Emily Hunter, Meggie Danielson, Mizue Terai, Philip B. Wedegaertner, Takami Sato, Solange Landreville, Michael A. Davies, Stefan Kurtenbach, J. William Harbour, Zachary T. Schug, Andrew E. Aplin
Summary: Metastatic uveal melanoma is difficult to treat, but targeting metabolic pathways, such as lipid/fat metabolism and mTOR, may be a potential therapeutic approach. The upregulation of enzymes involved in lipid/fat metabolism, such as FASN, and activation of the mTOR pathway were observed in uveal melanoma cells. Inhibiting FASN and mTOR led to the suppression of uveal melanoma cell growth, suggesting a novel treatment strategy for uveal melanoma.
Article
Oncology
Yan Zhang, Baoyuan Zhang, Yongyun Li, Yuting Dai, Jiaoyang Li, Donghe Li, Zhizhou Xia, Jianming Zhang, Ping Liu, Ming Chen, Bo Jiao, Ruibao Ren
Summary: The palmitoylation of GNAQ/11 plays a critical role in cell survival and proliferation in uveal melanoma (UM). The loss of GNAQ/11 palmitoylation cannot rescue the cell death initiated by the knock down of GNAQ/11 oncogenes in UM cells, which are more dependent on G alpha(q/11) signaling compared to other melanoma cells without GNAQ/11 mutations.
FRONTIERS OF MEDICINE
(2022)
Article
Oncology
Rui Wang, Houda Tahiri, Chun Yang, Solange Landreville, Sonia Callejo, Pierre Hardy
Summary: Uveal melanoma (UM) is the most common primary intraocular malignant tumor type in adults. Previous studies have shown that GNAQ/11 mutations are present in more than 85% of patients with UM, indicating their importance in UM occurrence. In this study, miR-181a-5p was found to effectively inhibit the viability, proliferation, and colony formation of UM cells, as well as induce apoptosis. Silencing GNAQ or AKT3 mimicked the anti-tumor effects of miR-181a-5p, while overexpression of GNAQ or AKT3 rescued these effects. MiR-181a-5p also suppressed the expression and phosphorylation of members of the ERK and PI3K/AKT/mTOR signaling pathways.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Medicine, Research & Experimental
Matthew L. Bendall, Jasmine H. Francis, Alexander N. Shoushtari, Douglas F. Nixon
Summary: The study identified four HERV-based subgroups in uveal melanoma, providing clear delineation of risk outcome and supporting other molecular subtypes. Intergenic HERVs with coding potential may represent potential therapeutic targets in tumor classification.
Article
Oncology
Michelle Prasuhn, Josephine Christin Freitag, Sabine Lueken, Vinodh Kakkassery, Hartmut Merz, Almuth Caliebe, Malte Spielmann, Mahdy Ranjbar, Felix Rommel
Summary: This case report describes the progression of a malignant uveal melanoma patient, who achieved successful tumor regression after plaque brachytherapy but experienced ring-shaped recurrence after 1 year, leading to enucleation. Histological and molecular genetic analyses revealed previously unreported GNAQ and SF3B1 gene mutations in this type of melanoma.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Ernesto Rossi, Michela Croce, Francesco Reggiani, Giovanni Schinzari, Marianna Ambrosio, Rosaria Gangemi, Giampaolo Tortora, Ulrich Pfeffer, Adriana Amaro
Summary: Survival rates for metastatic uveal melanoma have not significantly improved over the years, as it differs from cutaneous melanoma and is resistant to current therapies. The main obstacles are the activation of oncogenic signaling pathways that cannot be targeted, the lack of tumor specific neo-antigens for immune response, and the pro-tumorigenic microenvironment that promotes tumor progression. However, new drugs targeting oncogenic pathways, innovative immune therapy approaches, and liver-specific treatments offer hope for improving outcomes.
Review
Oncology
Rino S. Seedor, Marlana Orloff, Takami Sato
Summary: Uveal melanoma presents unique genetic landscape, potentially offering insights for prognosis and treatment. Current knowledge is primarily based on primary cases, highlighting the need for a better understanding of the mutational landscape in metastatic cases. Ongoing clinical trials targeting specific mutations have shown promise in this field.
