N-myc amplification and its relationship to experimental therapy.

N-myc amplification correlates with poor prognosis in neuroblastoma patients. Although the reason for this is unclear, it is possible that amplified N-myc confers resistance to certain agents used in the therapy of the disease. The acquisition of resistance to cytotoxic drugs in human tumor cells is multifactorial. One mechanism involved in the development of drug resistance is an increased efficiency of DNA repair. This could reduce the effectiveness of both cisplatin and etoposide (VP-16). Previous studies on human neuroblastoma cells have shown a relationship between N-myc copy number and cisplatin sensitivity. We now report the response to VP-16 treatment of five human neuroblastoma cell lines with a range of N-myc gene copy numbers. After exposure of cells to drug for 24 hours, survival curves were constructed from clonogenic assay data and the iso-effective dose (the dose required to produce 1 log cell kill) was derived. The relationship between N-myc copy number or expression and response to VP-16 was assessed. A significant correlation was established between VP-16 resistance and copy number (r = 0.82; P < 0.05). However, no association was found between N-myc expression and isoeffective dose of VP-16. These results indicate that N-myc amplification may be responsible for treatment failure in those patients receiving cisplatin or VP-16.