BRAF and neoplasm: Subsequently, preclinical studies demonstrated a decreased sensitivity to BRAF inhibitors with transient suppression of phosphorylated ERK, followed by the reactivation of RAS and C-RAF, mediated by the EGFR pathway. The combination of BRAF and EGFR inhibitors had a synergistic effect in vitro, resulting in sustained suppression of the MAPK pathway and the improvement of the efficacy of tumour growth inhibition [45].