Despite advances in the diagnosis and local tumor control, the overall mortality rate for uveal melanoma remains high because of the development of metastatic disease. The clinical and histopathological systems currently being used to classify patients are not sufficiently accurate to predict metastasis. Tumor genotyping has demonstrated significant promise but obtaining tumor tissue can be problematic. Furthermore, assessment of tumor tissue does not indicate whether tumor cells have actually been shed and cannot indicate whether treatment is reducing metastasis. The detection of circulating tumor cells in blood has been shown to be a prognostic biomarker that can be used to monitor the effectiveness of therapy in patients with metastatic carcinoma. Uveal melanoma disseminates hematogenously, and the detection of circulating melanoma cells may potentially be useful for diagnosis, risk stratification, and the monitoring of disease progression and treatment efficacy. PCR-based and immunomagnetic cell isolation techniques, derived from studies in patients with cutaneous melanoma, have been tested. For various biological and technical reasons, they have not demonstrated the accuracy and reproducibility required for an effective prognostic assay in patients with uveal melanoma. Assessments have been confounded by false positives and negatives and thus, correlations between circulating melanoma cells and survival have not yet been established. Circulating melanoma cell detection is a valuable tool for investigating metastasis in uveal melanoma and also has the potential to become a standard part of uveal melanoma management. However, more research on the biology of uveal melanoma as well as improvements upon the current technologies are needed.
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http://dx.doi.org/10.2217/fon.10.143 | DOI Listing |
Biochim Biophys Acta Rev Cancer
January 2025
Havener Eye Institute, Department of Ophthalmology and Visual Science, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; Division of Human Genetics, Department of Internal Medicine, The Ohio State University Columbus, OH 43210, USA. Electronic address:
BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that was first identified in 1998. Germline loss of functional variants in BAP1 is associated with a tumor predisposition syndrome with at least four cancers; uveal melanoma (UM), malignant mesothelioma (MMe), renal cell carcinoma (RCC), and cutaneous melanoma (CM). Furthermore, somatic BAP1 mutations are important drivers for several cancers most notably UM, MMe, RCC, intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC).
View Article and Find Full Text PDFBMC Biol
January 2025
Cancer Research Program, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Background: Uveal melanoma (UM) is the most common intraocular tumor in adults, arises either de novo from normal choroidal melanocytes (NCMs) or from pre-existing nevi that stem from NCMs and are thought to harbor UM-initiating mutations, most commonly in GNAQ or GNA11. However, there are no commercially available NCM cell lines, nor is there a detailed protocol for developing an oncogene-mutated CM line (MutCM) to study UM development. This study aimed to establish and characterize premalignant CM models from human donor eyes to recapitulate the cell populations at the origin of UM.
View Article and Find Full Text PDFJCO Precis Oncol
January 2025
Department of Medical Oncology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.
Purpose: Precision medicine plays an important role in the treatment of patients with advanced melanoma. Despite its high incidence in White patients, advanced melanoma is rare in Asian countries, hampering prospective clinical trials targeting the Asian population. This retrospective study aimed to elucidate the real-world molecular diagnoses and outcomes of Japanese patients with melanoma using comprehensive genome profiling (CGP).
View Article and Find Full Text PDFJ Immunother Precis Oncol
February 2025
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Introduction: Uveal melanoma remains a disease with aggressive behavior and poor prognosis despite advances in clinical management. Because monotherapy with immune checkpoint inhibitors has led to limited improvement in response rates, combination with other agents that act on the biological basis of oncogenesis has been proposed as a possible therapeutic strategy.
Methods: We designed a phase 1b trial to test the safety and tolerability of selinexor in combination with immune checkpoint inhibitors in patients with advanced uveal melanoma.
Acta Pharm Sin B
December 2024
Department of Ophthalmology, the First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Uveal melanoma (UM) poses a significant lethality, with approximately 50% of those developing metastases surviving less than one year. In the progression of UM, vasculogenic mimicry (VM) induced by hypoxia plays a pivotal role, which also partially explains the resistance of UM to anti-angiogenic therapies. Nevertheless, the crucial molecular mechanisms underlying VM in the progression of UM remain unclear.
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