title: 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 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.
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China.|Department of Gastroenterology, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, China.
authors.forename: Guihua
authors.initials: G
authors.lastname: Duan
authors.affiliation: National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, 210093, China.|Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210093, China.
authors.forename: Qianyuan
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Laboratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Special Medical Treatment, First Affiliated Hospital of Kunming Medical University, Kunming, 650332, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China.
authors.forename: Xi Emily
authors.initials: XE
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China.
authors.forename: Yuzheng
authors.initials: Y
authors.lastname: Zhuge
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China.
authors.forename: Xiaoqi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, 210093, China. wangj@nju.edu.cn.|Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210093, China. wangj@nju.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: National Laboratory of Solid State Microstructure, Department of Physics, Nanjing University, Nanjing, 210093, China. wangwei@nju.edu.cn.|Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing, 210093, China. wangwei@nju.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China. 13770771661@163.com.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology*; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D004358:Drug Therapy / Q000379:methods*; D064593:Heterografts; D006801:Humans; D051379:Mice; D008962:Models, Theoretical; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin