Modelling of the RAS-RAF-MEK-ERK pathway in hepatocellular cells exposed to sorafenib

par Mme Anne-Sophie Giacobbi (Université de Picardie Jules Verne)

mardi 10 janv. 2017, 11:00 → 12:00 Europe/Paris

432 (4ème étage) (INRIA- antenne Lyon- La Doua, Bâtiment CEI-2 (tram: T1-IUT FEYSSINE))

The RAS-RAF-MEK-ERK pathway is an important signal transduction cascade that is found activated in many types of human tumours. The hepatocellular carcinoma (HCC), the most frequent form of primary liver tumour, is a cancer with one of the worst prognoses, partially due to the small number of efficient therapeutic strategies. In order to design a more efficient strategy against cancer cells, further knowledge about the aspect of dynamic regulation of the RAS-RAF-MEK-ERK cascade is required. We decided to investigate the dynamic regulation of the RAS-RAF-MEK-ERK cascade in HCC cells exposed to sorafenib by using a systems biology approach. First, a mathematical model based on the Michaelis-Menten equation will be introduced to analyse the dynamic regulation of BRAF, CRAF, MEK and ERK. The results of the sensitivity analyse and the model prediction provided new insights on the therapeutic target. In a second time, the model will be extended to the all components set of the RAS-RAF-MEK-ERK pathway. The first results of the model prediction will be presented.