A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells
Abstract Cisplatin (ddp), which is commonly employed in the treatment of many advanced cancers, often results in initial therapeutic success; however, rapid progression of ddp-resistant cells remains the main reason for treatment failure. Facd with such a problem, we investigated the fitness differe...
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2017
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oai:doaj.org-article:a691dcdfe7174ca6ac4ff787ab00831c2021-12-02T12:32:17ZA Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells10.1038/s41598-017-00422-22045-2322https://doaj.org/article/a691dcdfe7174ca6ac4ff787ab00831c2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00422-2https://doaj.org/toc/2045-2322Abstract Cisplatin (ddp), which is commonly employed in the treatment of many advanced cancers, often results in initial therapeutic success; however, rapid progression of ddp-resistant cells remains the main reason for treatment failure. Facd with such a problem, we investigated the fitness differences between ddp-sensitive and ddp-resistant cell lines. We found that the growth of ddp-resistant cells was significantly slower than that of sensitive cells due to elevated ROS levels, which suggested that the ddp resistance mechanisms may have negative impacts on the growth of resistant cells. Furthermore, we observed that, when mixed with ddp-sensitive cells, ddp-resistant cells failed to compete, and the growth of ddp-resistant cells could therefore be suppressed by treatment in vivo. We propose a mathematical model parameterized based on in vivo experiments to describe the allometric growth of tumors consisting of two competing subclones. According to our model, a quantitative strategy with a variant drug-dosing interval is proposed to control tumor growth. Taking advantage of intratumoral competition, our strategy with appropriate dosing intervals could remarkably delay the development of ddp resistance and prolong overall survival. Maintaining a certain number of ddp-sensitive cells rather than eradicating the tumor with continuous treatment is feasible for future tumor treatment.Guihua DuanQianyuan TangHongli YanLijuan XieYun WangXi Emily ZhengYuzheng ZhugeShanshan ShenBin ZhangXiaoqi ZhangJun WangWei WangXiaoping ZouNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
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Medicine R Science Q Guihua Duan Qianyuan Tang Hongli Yan Lijuan Xie Yun Wang Xi Emily Zheng Yuzheng Zhuge Shanshan Shen Bin Zhang Xiaoqi Zhang Jun Wang Wei Wang Xiaoping Zou A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells |
| description |
Abstract Cisplatin (ddp), which is commonly employed in the treatment of many advanced cancers, often results in initial therapeutic success; however, rapid progression of ddp-resistant cells remains the main reason for treatment failure. Facd with such a problem, we investigated the fitness differences between ddp-sensitive and ddp-resistant cell lines. We found that the growth of ddp-resistant cells was significantly slower than that of sensitive cells due to elevated ROS levels, which suggested that the ddp resistance mechanisms may have negative impacts on the growth of resistant cells. Furthermore, we observed that, when mixed with ddp-sensitive cells, ddp-resistant cells failed to compete, and the growth of ddp-resistant cells could therefore be suppressed by treatment in vivo. We propose a mathematical model parameterized based on in vivo experiments to describe the allometric growth of tumors consisting of two competing subclones. According to our model, a quantitative strategy with a variant drug-dosing interval is proposed to control tumor growth. Taking advantage of intratumoral competition, our strategy with appropriate dosing intervals could remarkably delay the development of ddp resistance and prolong overall survival. Maintaining a certain number of ddp-sensitive cells rather than eradicating the tumor with continuous treatment is feasible for future tumor treatment. |
| format |
article |
| author |
Guihua Duan Qianyuan Tang Hongli Yan Lijuan Xie Yun Wang Xi Emily Zheng Yuzheng Zhuge Shanshan Shen Bin Zhang Xiaoqi Zhang Jun Wang Wei Wang Xiaoping Zou |
| author_facet |
Guihua Duan Qianyuan Tang Hongli Yan Lijuan Xie Yun Wang Xi Emily Zheng Yuzheng Zhuge Shanshan Shen Bin Zhang Xiaoqi Zhang Jun Wang Wei Wang Xiaoping Zou |
| author_sort |
Guihua Duan |
| title |
A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells |
| title_short |
A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells |
| title_full |
A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells |
| title_fullStr |
A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells |
| title_full_unstemmed |
A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells |
| title_sort |
strategy to delay the development of cisplatin resistance by maintaining a certain amount of cisplatin-sensitive cells |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/a691dcdfe7174ca6ac4ff787ab00831c |
| work_keys_str_mv |
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1718394112017694720 |