Cancer cells acquire resistance to anticancer drugs: an update
Hsing-Pang Lu1, Chuck C K Chao
1Department of Biochemistry and Molecular Biology, and Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Abstract:
The efficacy of cancer chemotherapy is often affected by the emergence of resistant can-cer cells. While biochemical and pharmaco-logical mechanisms have been proposed to ex-plain chemo-resistance, the genes involved in this process have not been fully identified. We previously used genomic DNA microarrays and quantitative RT-PCR to identify the genes associated with resistance to chemotherapeutic drugs, particularly to the genotoxic agent cisplatin. Notably, knockdown of the cisplatin resistance (CPR) genes that we identified was shown to reduce chemoresistance and to suppress the growth of tumor xenographs in cisplatin-treated mice, indicating that the newly identified CPR genes may represent potential therapy candidates to limit chemo-resistance and to improve the efficacy of anticancer drugs. In addition to genetic mutations, re-searchers have found that epigenetic changes and alternative splicing of specific genes may also allow cancer cells to become resistant to chemotherapeutic drugs. In this article, the authors present an overview of the latest findings in this field, including genetic changes, epigenetic changes and alternative splicing.
Insights
Identifying genes involved in cancer drug resistance is crucial for improving chemotherapy. New cisplatin resistance (CPR) genes were found to reduce chemoresistance and tumor growth, offering potential new therapies.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Chemotherapy efficacy is frequently limited by the development of drug-resistant cancer cells.
- While mechanisms of chemoresistance are studied, the specific genes involved remain largely unidentified.
- Genetic mutations, epigenetic alterations, and alternative splicing are implicated in cancer cell resistance.
Purpose of the Study:
- To identify novel genes associated with chemoresistance, particularly to cisplatin.
- To investigate the therapeutic potential of targeting identified chemoresistance genes.
Main Methods:
- Genomic DNA microarrays were employed to screen for genes linked to cisplatin resistance.
- Quantitative RT-PCR was used for gene validation.
- The functional role of identified genes was assessed through gene knockdown experiments in mice models.
Main Results:
- Several cisplatin resistance (CPR) genes were identified.
- Knockdown of these CPR genes significantly reduced chemoresistance in cancer cells.
- Suppression of tumor xenograft growth was observed in cisplatin-treated mice following CPR gene knockdown.
Conclusions:
- The identified CPR genes are critical mediators of cisplatin resistance.
- Targeting these CPR genes presents a promising therapeutic strategy to overcome chemoresistance.
- These findings may lead to improved efficacy of anticancer drugs and better patient outcomes.
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