The MYC oncogene as a cancer drug target.
The universal deregulation of c-myc gene expression in tumor cells suggests that this oncogene represents an attractive target for cancer therapeutic purposes. The same applies to the N-myc gene, which has a more restricted tissue specificity. Translocation (e.g., c-myc in Burkitt's lymphoma), or amplification (e.g., N-myc in neuroblastoma) of myc genes has been causally linked to tumor formation. Furthermore, the c-myc promoter integrates diverse mitogenic signalling cascades, which are constitutively activated in tumor cells, and translates them into expression of the c-MYC transcription factor, which promotes cell proliferation by regulating the expression of numerous target genes. Recent experimental data suggest, that even a brief inhibition of c-myc expression may be sufficient to permanently stop tumor growth and induce regression of tumors. Attempts to identify specific inhibitors of c-MYC/MAX dimerization have yielded promising results. In addition, downstream-target genes of c-MYC represent attractive targets for tumor therapy. Tumor cells expressing c-MYC at elevated levels are sensitized to treatment with DNA-damaging drugs. In mice and presumably also in human patients, the successful treatment of c-myc-induced tumors with conventional chemotherapy depends on the presence of functional p53. Therefore, restoration of this pathway, which is commonly lost in cancer cells, may enhance therapy of c-myc-induced tumors. These and other recent developments, which address the use of myc genes as therapeutic targets for cancer treatment, are discussed in this review.
Hermeking
Heiko
H
Molecular Oncology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18A, D-82152 Martinsried, Germany. herme@biochem.mpg.de
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D016259:Genes, myc / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use
D020319:Oligodeoxyribonucleotides, Antisense