TNF-α inhibitor reduces drug-resistance to anti-PD-1: A mathematical model

Xiulan Lai, Wenrui Hao, Avner Friedman

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Drug resistance is a primary obstacle in cancer treatment. In many patients who at first respond well to treatment, relapse occurs later on. Various mechanisms have been explored to explain drug resistance in specific cancers and for specific drugs. In this paper, we consider resistance to anti-PD-1, a drug that enhances the activity of anti-cancer T cells. Based on results in experimental melanoma, it is shown, by a mathematical model, that resistances to anti-PD-1 can be significantly reduced by combining it with anti-TNF-α. The model is used to simulate the efficacy of the combined therapy with different range of doses, different initial tumor volume, and different schedules. In particular, it is shown that under a course of treatment with 3-week cycles where each drug is injected in the first day of either week 1 or week 2, injecting anti-TNF-α one week after anti-PD-1 is the most effective schedule in reducing tumor volume.

Original languageEnglish (US)
Article numbere0231499
JournalPloS one
Issue number4
StatePublished - Apr 2020

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • General


Dive into the research topics of 'TNF-α inhibitor reduces drug-resistance to anti-PD-1: A mathematical model'. Together they form a unique fingerprint.

Cite this