TY - JOUR
T1 - TNF-α inhibitor reduces drug-resistance to anti-PD-1
T2 - A mathematical model
AU - Lai, Xiulan
AU - Hao, Wenrui
AU - Friedman, Avner
N1 - Publisher Copyright:
© 2020 Lai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/4
Y1 - 2020/4
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0231499
DO - 10.1371/journal.pone.0231499
M3 - Article
C2 - 32310956
AN - SCOPUS:85083496703
SN - 1932-6203
VL - 15
JO - PloS one
JF - PloS one
IS - 4
M1 - e0231499
ER -