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Tumor suppressor genes and their underlying interactions in paclitaxel resistance in cancer therapy
Jia-Hui Xu1, Shi-Lian Hu1, Guo-Dong Shen1
1Department of Geriatrics, Anhui Provincial Hospital affiliated to Anhui Medical University, 17 Lujiang Road, Hefei, 230001 China ; Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei, 230001 China.
Objectives:
Paclitaxel (PTX) is frequently used in the clinical treatment of solid tumors. But the PTX-resistance is a great obstacle in cancer treatment. Exploration of the mechanisms of drug resistance suggests that tumor suppressor genes (TSGs) play a key role in the response of chemotherapeutic drugs. TSGs, a set of genes that are often inactivated in cancers, can regulate various biological processes. In this study, an overview of the contribution of TSGs to PTX resistance and their underlying relationship in cancers are reported by using GeneMANIA, a web-based tool for gene/protein function prediction.
Methods:
Using PubMed online database and Google web site, the terms "paclitaxel resistance" or "taxol resistance" or "drug resistance" or "chemotherapy resistance", and "cancer" or "carcinoma", and "tumor suppressor genes" or "TSGs" or "negative regulated protein" or "antioncogenes" were searched and analyzed. GeneMANIA data base was used to predict gene/protein interactions and functions.
Results:
We identified 22 TSGs involved in PTX resistance, including BRCA1, TP53, PTEN, APC, CDKN1A, CDKN2A, HIN-1, RASSF1, YAP, ING4, PLK2, FBW7, BLU, LZTS1, REST, FADD, PDCD4, TGFBI, ING1, Bax, PinX1 and hEx. The TSGs were found to have direct and indirect relationships with each other, and thus they could contribute to PTX resistance as a group. The varied expression status and regulation function of the TSGs on cell cycle in different cancers might play an important role in PTX resistance.
Conclusion:
A further understanding of the roles of tumor suppressor genes in drug resistance is an important step to overcome chemotherapy tolerance. Tumor suppressor gene therapy targets the altered genes and signaling pathways and can be a new strategy to reverse chemotherapy resistance.
Insights
Tumor suppressor genes (TSGs) are crucial in paclitaxel (PTX) resistance in cancers. Understanding these gene networks offers new strategies to overcome chemotherapy resistance and improve cancer treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Paclitaxel (PTX) is a key chemotherapy drug for solid tumors.
- Paclitaxel resistance significantly hinders effective cancer treatment.
- Tumor suppressor genes (TSGs) are critical regulators often inactivated in cancer and influence drug response.
Purpose of the Study:
- To investigate the role and interrelationships of tumor suppressor genes (TSGs) in paclitaxel resistance.
- To provide an overview of TSGs contributing to paclitaxel resistance in various cancers.
- To explore the potential of targeting TSGs for overcoming chemotherapy resistance.
Main Methods:
- Literature search using PubMed and Google for terms related to paclitaxel resistance and TSGs.
- Analysis of gene and protein interactions and functions using the GeneMANIA web tool.
Main Results:
- Identified 22 TSGs implicated in paclitaxel resistance, including BRCA1, TP53, and PTEN.
- Demonstrated that these TSGs are interconnected, collectively contributing to paclitaxel resistance.
- Highlighted the role of varied TSG expression and cell cycle regulation in different cancers' resistance mechanisms.
Conclusions:
- Understanding TSG involvement in drug resistance is vital for overcoming chemotherapy tolerance.
- Targeting TSGs and their pathways presents a promising therapeutic strategy to reverse paclitaxel resistance.
- Further research into TSG networks can lead to novel approaches in cancer therapy.
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