FR900359 and Uveal-Neoplasms

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.

Topics: Antineoplastic Agents; Clinical Trials as Topic; Depsipeptides; Genetic Predisposition to Disease; GTP-Binding Protein alpha Subunits; GTP-Binding Protein alpha Subunits, Gq-G11; Humans; Melanoma; Mutation; Neoplasm Metastasis; Receptors, G-Protein-Coupled; Signal Transduction; Uveal Neoplasms

Access to the cyclic depsipeptide FR900359 (FR), a selective G

Topics: Cell Line, Tumor; Chromobacterium; Depsipeptides; GTP-Binding Protein alpha Subunits, Gq-G11; Humans; Mutation; Promoter Regions, Genetic; Uveal Neoplasms

Uveal melanoma is the most common intraocular tumor in adults and often metastasizes to the liver, leaving patients with few options. Recurrent activating mutations in the G proteins, Gα

Topics: Animals; Cell Growth Processes; Cell Line, Tumor; Depsipeptides; GTP-Binding Protein alpha Subunits; GTP-Binding Protein alpha Subunits, Gq-G11; Guanosine 5'-O-(3-Thiotriphosphate); Humans; Insecta; MAP Kinase Signaling System; Melanoma; Rats; Recombinant Proteins; Uveal Neoplasms

Somatic gain-of-function mutations of

Topics: Animals; Cell Line, Tumor; Depsipeptides; Drug Delivery Systems; Gain of Function Mutation; GTP-Binding Protein alpha Subunits; GTP-Binding Protein alpha Subunits, Gq-G11; HEK293 Cells; Humans; Melanoma; Mice; Mice, Inbred NOD; Mice, SCID; Neoplasm Proteins; Uveal Neoplasms; Xenograft Model Antitumor Assays