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Overcoming Drug Resistance to BRAF Inhibitor

  • Avner Friedman
  • Nourridine SieweEmail author
Original Article

Abstract

One of the most frequently found mutations in human melanomas is in the B-raf gene, making its protein BRAF a key target for therapy. However, in patients treated with BRAF inhibitor (BRAFi), although the response is very good at first, relapse occurs within 6 months, on the average. In order to overcome this drug resistance to BRAFi, various combinations of BRAFi with other drugs have been explored, and some are being applied clinically, such as a combination of BRAF and MEK inhibitors. Experimental data for melanoma in mice show that under continuous treatment with BRAFi, the pro-cancer MDSCs and chemokine CCL2 initially decrease but eventually increase to above their original level, while the anticancer T cells continuously decrease. In this paper, we develop a mathematical model that explains these experimental results. The model is used to explore the efficacy of combinations of BRAFi with anti-CCL2, anti-PD-1 and anti-CTLA-4, with the aim of eliminating or reducing drug resistance to BRAFi.

Keywords

Metastatic melanoma cancer Checkpoint inhibitors BRAF inhibitor resistance 

Notes

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Copyright information

© Society for Mathematical Biology 2020

Authors and Affiliations

  1. 1.Mathematical Biosciences Institute & Department of MathematicsThe Ohio State UniversityColumbusUSA
  2. 2.Department of MathematicsThe University of British Columbia OkanaganKelownaCanada

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