Skip to main content
padlock icon - secure page this page is secure

The MYCN Oncogene as a Specific and Selective Drug Target for Peripheral and Central Nervous System Tumors

Buy Article:

$68.00 + tax (Refund Policy)

MYCN belongs to the MYC family of proto-oncogenes, which encode for transcription factors of the basic-helix-loop-helix-zipper (bHLHZ) class and is fundamental in the development of the peripheral and central nervous systems (PNS and CNS). While Myc is ubiquitous, MYCN has a very restricted expression pattern: it is mainly expressed during embryonic development, but then becomes downregulated, while in adults it is usually detected in B-cell development. Identification of selective inhibitors of MYCN and its mRNA and protein could be important for the development of more specific, effective and less toxic therapeutic agents for tumors of the PNS and CNS.

In children, the most common tumors of the PNS and CNS are neuroblastomas and medulloblastomas, respectively. About 30% of neuroblastoma (NB) tumors present MYCN amplification/over-expression, which is associated with rapid progression and poor prognosis. N-Myc is essential during neurogenesis for the rapid expansion of progenitor cells in the brain. MYCN amplification and over-expression has been reported in medulloblastoma, and especially in the desmoplastic type. Other tumors associated with MYCN overexpression include retinoblastoma, small cell lung carcinoma, glioblastoma and certain embryonal tumors.

A cell-based, N-Myc-dependent luciferase reporter gene assay to identify specific N-Myc small-molecule inhibitors has allowed identification of five compounds showing significant activity. Antisense oligodeoxynucleotides have been shown to inhibit N-Myc production and anti-tumoral activity in vitro and in vivo for NB. Peptide nucleic acids (PNA), which belong to the most recent (third) generation of nucleic acid therapeutics, form highly stable duplexes with DNA and RNA, and are resistant to degradation by nucleases and proteases. Encouraging results have been reported utilizing a PNA-based antisense strategy for inhibition of N-Myc expression in neuroblastoma.
No References
No Citations
No Supplementary Data
No Article Media
No Metrics

Keywords: antisense oligonucleotides; gene amplification; immunotherapy; mycn; neuronal tumors; peptide nucleic acids; small molecules; triplex forming oligonucleotides

Document Type: Review Article

Affiliations: Unita Oncoematologia pediatrica e Terapia Cellulare, Dipartimento di Scienze Pediatriche Mediche e Chirurgiche, Policlinico S. Orsola-Malpighi, via Massarenti 11, 40138 Bologna, Italy.

Publication date: June 1, 2005

More about this publication?
  • Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes, genes.
    Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cancer.
    As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
  • Editorial Board
  • Information for Authors
  • Subscribe to this Title
  • Ingenta Connect is not responsible for the content or availability of external websites
  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more