title: Therapeutic implications of the emerging molecular biology of uveal melanoma.
abstract: Uveal melanoma represents the most common primary intraocular malignancy in adults. Although uveal and cutaneous melanomas both arise from melanocytes, uveal melanoma is clinically and biologically distinct from its more common cutaneous counterpart. Metastasis occurs frequently in this disease, and once distant spread occurs, outcomes are poor. No effective systemic therapies are currently available; however, recent advances in our understanding of the biology of this rare and devastating disease, combined with the growing availability of targeted agents, which can be used to rationally exploit these findings, hold the promise for novel and effective therapies in the foreseeable future. Herein, we review our rapidly growing understanding of the molecular biology of uveal melanoma, including the pathogenic roles of GNAQ (guanine nucleotide binding protein q polypeptide)/11, PTEN (phosphatase and tensin homolog), IGF (insulin-like growth factor)/IGF-1 receptor, MET (hepatocyte growth factor), BAP1 [breast cancer 1, early onset (BRCA1)-associated protein-1], and other key molecules, potential therapeutic strategies derived from this emerging biology, and the next generation of recently initiated clinical trials for the treatment of advanced uveal melanoma.
authors: Department of Medicine and Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
authors: Mrinali
authors: M
authors: Patel
authors: Elizabeth
authors: E
authors: Smyth
authors: Paul B
authors: PB
authors: Chapman
authors: Jedd D
authors: JD
authors: Wolchok
authors: Gary K
authors: GK
authors: Schwartz
authors: David H
authors: DH
authors: Abramson
authors: Richard D
authors: RD
authors: Carvajal
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000098943:Uveal Melanoma
chemical_list: D000970:Antineoplastic Agents; C554062:GNA11 protein, human; D044385:GTP-Binding Protein alpha Subunits; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases