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A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells(Open Access)

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机构： [1]Department of Gastroenterology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008,China [2]Department of Gastroenterology, The First People’s Hospital of Yunnan Province, The Affiliated Hospitalof Kunming University of Science and Technology, Kunming, 650032, China [3]National Laboratory of Solid StateMicrostructure, Department of Physics, Nanjing University, Nanjing, 210093, China [4]Collaborative InnovationCenter of Advanced Microstructures, Nanjing University, Nanjing, 210093, China [5]Department of LaboratoryMedicine, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China [6]Department of SpecialMedical Treatment, First Affiliated Hospital of Kunming Medical University, Kunming, 650332, China

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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. © 2017 The Author(s).

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出版当年[2017]版：

大类 | 3 区综合性期刊

小类 | 3 区综合性期刊

最新[2023]版：

大类 | 2 区综合性期刊

小类 | 2 区综合性期刊

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出版当年[2016]版：

Q1 MULTIDISCIPLINARY SCIENCES

最新[2023]版：

Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 3.8 最新[2023版] 4.3 最新五年平均 4.259 出版当年[2016版] 4.847 出版当年五年平均 5.228 出版前一年[2015版] 4.122 出版后一年[2017版]

第一作者：

第一作者机构： [1]Department of Gastroenterology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008,China [2]Department of Gastroenterology, The First People’s Hospital of Yunnan Province, The Affiliated Hospitalof Kunming University of Science and Technology, Kunming, 650032, China

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通讯机构： [3]National Laboratory of Solid StateMicrostructure, Department of Physics, Nanjing University, Nanjing, 210093, China [4]Collaborative InnovationCenter of Advanced Microstructures, Nanjing University, Nanjing, 210093, China

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