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Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma
Published on: January 25, 2015
Dysregulated GPCR Signaling and Therapeutic Options in Uveal Melanoma
Vivian Chua1, Dominic Lapadula2, Clinita Randolph2
1Department of Cancer Biology, Sidney Kimmel Cancer Center at Jefferson, Thomas Jefferson University, Philadelphia, Pennsylvania.
Abstract:
Uveal melanoma is the most common primary intraocular malignant tumor in adults and arises from the transformation of melanocytes in the uveal tract. Even after treatment of the primary tumor, up to 50% of patients succumb to metastatic disease. The liver is the predominant organ of metastasis. There is an important need to provide effective treatment options for advanced stage uveal melanoma. To provide the preclinical basis for new treatments, it is important to understand the molecular underpinnings of the disease. Recent genomic studies have shown that mutations within components of G protein-coupled receptor (GPCR) signaling are early events associated with approximately 98% of uveal melanomas.Implications: This review discusses the alterations in GPCR signaling components (GNAQ and GNA11), dysregulated GPCR signaling cascades, and viable targeted therapies with the intent to provide insight into new therapeutic strategies in uveal melanoma. Mol Cancer Res; 15(5); 501-6. ©2017 AACR.
Insights
Uveal melanoma, a common eye cancer, often metastasizes to the liver. Understanding mutations in G protein-coupled receptor (GPCR) signaling pathways is key to developing new targeted therapies for advanced disease.
Area of Science:
- Oncology
- Molecular Biology
- Ophthalmology
Background:
- Uveal melanoma is the most frequent primary intraocular malignancy in adults.
- Metastatic disease, primarily to the liver, affects up to 50% of patients post-treatment.
- Effective treatments for advanced uveal melanoma are urgently needed.
Purpose of the Study:
- To review the molecular underpinnings of uveal melanoma, focusing on G protein-coupled receptor (GPCR) signaling.
- To discuss targeted therapies for uveal melanoma based on GPCR alterations.
- To provide insights into novel therapeutic strategies for advanced uveal melanoma.
Main Methods:
- Genomic studies identifying mutations in GPCR signaling components.
- Review of dysregulated GPCR signaling cascades in uveal melanoma.
- Analysis of potential targeted therapies for GPCR-driven uveal melanoma.
Main Results:
- Approximately 98% of uveal melanomas harbor mutations in GPCR signaling components.
- Specific mutations in GNAQ and GNA11 are early events in uveal melanoma development.
- Dysregulation of GPCR signaling pathways is a hallmark of uveal melanoma.
Conclusions:
- Targeting altered GPCR signaling pathways offers a promising therapeutic strategy for uveal melanoma.
- Understanding GNAQ and GNA11 mutations is crucial for developing effective treatments.
- Further research into targeted therapies is essential for improving outcomes in advanced uveal melanoma.
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