2016 Conference on Computational Modelling with COPASI
Manchester Institute of Biotechnology, 12th – 13th May, 2016

Systems modelling of integrated mTOR-MAPK networks for cancer therapy

William Postlethwaite1, Laura Corbett2, Kathrin Thedieck2, Daryl Shanley1

1 - Newcastle University, UK; 2 - Groningen University, The Netherlands

Keywords: PI3K/AKT/mTOR, MAPK/ERK, pathway crosstalk, individualised cancer therapy


Many cancers respond unpredictably to treatment, this is due to variation in the mutations that cause the cancer in each patient and compensatory signalling by pathways that are not targeted by the therapeutic agent. The overall aim of the project is to develop patient specific computational models in Copasi that will allow for treatment optimization. The PI3K/AKT/mTOR and MAPK/ERK pathways are common targets of a number of clinically relevant targeted therapies. Identifying treatment strategies to target the networks are complicated by feedbacks within the networks themselves and multiple levels of crosstalk between them. We are developing an integrated computational model to simulate the interplay between the mTOR and ERK signalling dynamics. We adopt a strategy to first model the mTOR and ERK networks separately followed by an interactive process to integrate them. This process is informed by kinetic data gathered in different cancer cell lines. The model will then be used to investigate the effect of crosstalk between the two pathways and ultimately be used to inform how each patients individual mutation profile affect treatment response allowing for treatment stratification.

Conference Program