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TNF-α inhibitor reduces drug-resistance to anti-PD-1: A mathematical model
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...
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Published in: | PloS one 2020-04, Vol.15 (4), p.e0231499-e0231499 |
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description | 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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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. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lai, Xiulan</au><au>Hao, Wenrui</au><au>Friedman, Avner</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TNF-α inhibitor reduces drug-resistance to anti-PD-1: A mathematical model</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-04-20</date><risdate>2020</risdate><volume>15</volume><issue>4</issue><spage>e0231499</spage><epage>e0231499</epage><pages>e0231499-e0231499</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Drug resistance is a primary obstacle in cancer treatment. 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subjects | Animals Anticancer properties Antigens Antineoplastic Combined Chemotherapy Protocols - pharmacology Apoptosis Biology and Life Sciences Cancer therapies Cell death Chemotherapy Computer simulation Cytokines Cytotoxicity Dendritic cells Drug resistance Drug Resistance, Neoplasm - drug effects Immunotherapy Kinases Ligands Lymphocytes Lymphocytes T Mathematical analysis Mathematical models Medicine and Health Sciences Melanoma Mice Models, Theoretical Mutation Neoplasm Recurrence, Local - drug therapy Neoplasm Recurrence, Local - metabolism Partial differential equations PD-1 protein Physical Sciences Programmed Cell Death 1 Receptor - antagonists & inhibitors Proteins Schedules Tumor Burden - drug effects Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor necrosis factor-α Tumors |
title | TNF-α inhibitor reduces drug-resistance to anti-PD-1: A mathematical model |
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