title: Dysregulated GPCR Signaling and Therapeutic Options in Uveal Melanoma.
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.
authors.affiliation: Department of Cancer Biology, Sidney Kimmel Cancer Center at Jefferson, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Vivian
authors.initials: V
authors.lastname: Chua
authors.affiliation: Department of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center at Jefferson, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Dominic
authors.initials: D
authors.lastname: Lapadula
authors.affiliation: Department of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center at Jefferson, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Clinita
authors.initials: C
authors.lastname: Randolph
authors.affiliation: Department of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center at Jefferson, Thomas Jefferson University, Philadelphia, Pennsylvania.|Cancer Cell Biology and Signaling Program, Sidney Kimmel Cancer Center at Jefferson, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Benovic
authors.affiliation: Department of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center at Jefferson, Thomas Jefferson University, Philadelphia, Pennsylvania.|Cancer Cell Biology and Signaling Program, Sidney Kimmel Cancer Center at Jefferson, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Philip B
authors.initials: PB
authors.lastname: Wedegaertner
authors.affiliation: Department of Cancer Biology, Sidney Kimmel Cancer Center at Jefferson, Thomas Jefferson University, Philadelphia, Pennsylvania. Andrew.Aplin@kimmelcancercenter.org.|Cancer Cell Biology and Signaling Program, Sidney Kimmel Cancer Center at Jefferson, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Aplin
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D002986:Clinical Trials as Topic; D047630:Depsipeptides / Q000008:administration & dosage / Q000494:pharmacology; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D009362:Neoplasm Metastasis; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014604:Uveal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D000098943:Uveal Melanoma
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; C000607068:FR900359; C554062:GNA11 protein, human; C554061:GNAQ protein, human; D044385:GTP-Binding Protein alpha Subunits; D043562:Receptors, G-Protein-Coupled; D043802:GTP-Binding Protein alpha Subunits, Gq-G11