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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

According to the Montreal classification, the disease extent determined at endoscopy can be classified into three subgroups: involvement limited to the rectum (E1), involvement limited to the distal colon not exceeding the splenic flexure (E2), or involvement exceeding the splenic flexure (E3) [4]