Myc proteins as therapeutic targets

• Published in: Oncogene Vol. 29; no. 9; pp. 1249 - 1259
• Main Authors: Gustafson, W C, Weiss, W A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.03.2010; Nature Publishing Group
• Subjects: 1-Phosphatidylinositol 3-kinase; 631/378/1689/1690; 631/45/612/1243; 631/67/1059/602; 692/699/67/2332; AKT protein; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; c-Myc protein; Care and treatment; Cell Biology; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular proteins; Cellular signal transduction; Chemotherapy; Child; Children; Drug Delivery Systems; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic - drug effects; Genes, myc - drug effects; Genes, myc - physiology; Genetic aspects; Genetics; Health aspects; Human Genetics; Humans; Internal Medicine; Kinases; MDM2 protein; Medical sciences; Medicine; Medicine & Public Health; Molecular and cellular biology; Myc protein; MYCN gene; Neuroblastoma; Neurology; Oncology; p53 Protein; Pediatrics; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphorylation; Physiological aspects; Protein kinases; Protein-tyrosine kinase receptors; Proteins; Proto-Oncogene Proteins c-myc - administration & dosage; Proto-Oncogene Proteins c-myc - pharmacology; review; Signal transduction; Signal Transduction - genetics; Solid tumors; Therapeutic targets; TOR protein; Transcriptional Activation - genetics; Tumors of the nervous system. Phacomatoses; Ubiquitin; United States; neuroblastoma; mTor; N-myc; mycn; PI3K; myc; Nervous system diseases; Malignant tumor; Neuroblastoma; Carcinogenesis; Protein; Autonomic neuropathy; Onc gene; Cancer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2009.512

Myc proteins (c-myc, Mycn and Mycl) target proliferative and apoptotic pathways vital for progression in cancer. Amplification of the MYCN gene has emerged as one of the clearest indicators of aggressive and chemotherapy-refractory disease in children with neuroblastoma, the most common extracranial solid tumor of childhood. Phosphorylation and ubiquitin-mediated modulation of Myc protein influence stability and represent potential targets for therapeutic intervention. Phosphorylation of Myc proteins is controlled in-part by the receptor tyrosine kinase/phosphatidylinositol 3-kinase/Akt/mTOR signaling, with additional contributions from Aurora A kinase. Myc proteins regulate apoptosis in part through interactions with the p53/Mdm2/Arf signaling pathway. Mutation in p53 is commonly observed in patients with relapsed neuroblastoma, contributing to both biology and therapeutic resistance. This review examines Myc function and regulation in neuroblastoma, and discusses emerging therapies that target Mycn.