Medicine and Health

Quantifying ERK activity in response to inhibition of the BRAFV600E-MEK-ERK cascade using mathematical modelling

S. J. Hamis, Y. Kapelyukh, et al.

This research, conducted by Sara J. Hamis and colleagues, unveils a groundbreaking mathematical model that quantifies ERK activity in BRAFV600E-mutant melanoma. The study reveals how the combination of BRAF and MEK inhibitors synergistically impacts ERK activity and highlights factors contributing to drug resistance, paving the way for optimized treatment strategies.

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Abstract

This paper presents a mechanistic mathematical model to quantify ERK activity in response to the combined inhibition of BRAF and MEK in BRAFV600E-mutant melanoma. The model, based on mass action kinetics and parameterized with in vitro data, simulates the dynamics of the BRAF-MEK-ERK signaling cascade under the influence of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor). The results show how these drugs synergistically inhibit ERK activity, and how elevated BRAF and ATP levels contribute to drug resistance. The model provides a tool to predict effective drug combinations for treating BRAFV600E-mutated melanoma.

Publisher

British Journal of Cancer

Published On

Oct 07, 2021

Authors

Sara J. Hamis, Yury Kapelyukh, Aileen McLaren, Colin J. Henderson, C. Roland Wolf, Mark A. J. Chaplain

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