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

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*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Article number432
Number of pages13
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 27 Mar 2017

Scopus Subject Areas

  • General

Fingerprint

Dive into the research topics of 'A Strategy to Delay the Development of Cisplatin Resistance by Maintaining a Certain Amount of Cisplatin-Sensitive Cells'. Together they form a unique fingerprint.

Cite this