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cDNA Technologies and their application to drug resistance research: power, potential and problems
Zhenfeng Duan1, Diana E. Lamendola, Michael V. Seiden
1Department of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA
Abstract:
The effectiveness of systemic chemotherapy is dramatically limited by both intrinsic and acquired drug resistance. Several new technologies have been developed over the last decade to more rapidly identify underlying genetic alterations that impart a drug-resistant phenotype. Techniques such as cDNA-based subtraction technologies, SAGE analysis, and most recently cDNA array and high-density micro-array technologies have rapidly expanded our ability to detect changes in RNA transcription in drug-resistant tumors. These technologies are currently being applied to generate a large number of new hypotheses regarding the regulatory molecules underlying the drug-resistance phenotype. These techniques suggest that there is a large number of transcriptional changes which occur in the drug-resistance phenotype and future work will need to focus on dissecting which of these transcriptional changes are central to the drug resistance phenotype, both in vitro, and more importantly within clinical neoplasia. Copyright 2000 Harcourt Publishers Ltd.
Insights
New technologies help identify genetic causes of chemotherapy drug resistance. Further research is needed to pinpoint key transcriptional changes in drug-resistant tumors for better cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Systemic chemotherapy effectiveness is limited by intrinsic and acquired drug resistance.
- Identifying genetic alterations driving drug resistance is crucial for improving cancer therapy.
Purpose of the Study:
- To review recent technological advancements in identifying genetic alterations responsible for drug resistance.
- To highlight the application of these technologies in understanding drug-resistant tumors.
Main Methods:
- Review of cDNA-based subtraction, SAGE analysis, cDNA array, and high-density microarray technologies.
- Analysis of their role in detecting RNA transcription changes in drug-resistant tumors.
Main Results:
- These technologies have significantly advanced the ability to detect transcriptional changes in drug-resistant tumors.
- A large number of transcriptional alterations are associated with the drug-resistance phenotype.
Conclusions:
- New technologies generate numerous hypotheses regarding molecules regulating drug resistance.
- Future research must focus on distinguishing central transcriptional changes from background alterations in vitro and in clinical settings.