Related Experiment Videos
Preclinical leads for innovative uses for etoposide
D D Von Hoff1, J McGill, K Davidson
1Department of Medicine, University of Texas Health Science Center, San Antonio 78284.
Seminars in Oncology
|December 1, 1992
Summary
The cancer drug etoposide significantly reduced double minutes (DMs) carrying amplified oncogenes in tumor cells. This finding suggests a potential strategy to decrease tumor aggressiveness by eliminating these amplified oncogenes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Amplification of oncogenes in human tumors correlates with poor prognosis.
- Amplified oncogenes can reside in chromosomal homogeneously staining regions or extrachromosomal double minutes (DMs).
- Extrachromosomal amplified oncogenes in DMs are susceptible to cellular loss.
Purpose of the Study:
- To investigate the effect of the topoisomerase II inhibitor etoposide on DM-containing amplified oncogenes.
- To determine if etoposide can reduce the number of amplified oncogenes located in DMs.
- To explore the potential therapeutic implications of eliminating amplified oncogenes.
Main Methods:
- Treatment of three human tumor cell lines with clinically achievable concentrations of etoposide.
- Quantification of the number of double minutes (DMs) containing amplified oncogenes before and after treatment.
- Assessment of changes in amplified oncogene copy number and cellular localization.
Main Results:
- Etoposide treatment led to a significant decrease in the number of DMs in all tested tumor cell lines.
- The reduction in DMs suggests a loss of extrachromosomal amplified oncogenes.
- The observed effect was achieved with clinically relevant concentrations of etoposide.
Conclusions:
- Etoposide effectively reduces extrachromosomal amplified oncogenes located in double minutes (DMs).
- Elimination of amplified oncogenes may lead to less aggressive tumor behavior.
- Targeting DMs with etoposide represents a potential therapeutic strategy in oncology.