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Although, CRCs are largely inert to BRAFi monotherapy still, combined RAF and EGFR inhibition is shown to have some clinical benefit ( Resistant in vitro models commonly established from Colo205, HT-29, VACO432 and RKO cell lines and patient-derived xenografts of progression samples were shown to be sensitive to combined treatment of BRAFi and AKTi (PLX4720/vemurafenib and MK-2206) ( 2.4.2 CNS tumors We are only beginning to understand resistance mechanisms in CNS tumors (103), mainly due to the scarcity of resistance models

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