Overcoming Drug Resistance to BRAF Inhibitor.

Publication date: Jan 14, 2020

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.

Friedman, A. and Siewe, N. Overcoming Drug Resistance to BRAF Inhibitor. 25451. 2020 Bull Math Biol (82):1.

Concepts Keywords
BRAF Medicine
BRAF Inhibitor Clinical medicine
Cancer Cancer treatments
CCL2 MEK inhibitor
Chemokine Melanoma
Drug Resistance BRAF
Gene CCL2
MEK Checkpoint inhibitor
Melanoma Vemurafenib
Melanomas Dabrafenib


Type Source Name
disease MESH melanomas
disease MESH relapse
pathway KEGG Melanoma
disease MESH cancer


Original Article

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