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04) [36]. BRAF mutations were not predictive, but were prognostic, with a shorter OS in the cohort harboring that mutation compared with patients with wild-type BRAF. Furthermore, a meta-analysis revealed that mutations in PIK3CA and inactivating mutations in PTENas well as KRASNRASand BRAF mutations, might all predict resistance to EGFR monoclonal antibodies [37]. BRAF mutations occur in 1015 of CRC and cause a constitutive activation of the mitogen-activated protein kinase ( MAPK ) pathway. BRAF mutations are associated with poor survival in microsatellite stable CRC but have less effect on the prognosis in MSI CRC. [38, 39] BRAF inhibitor ( BRAFi ) treatment has been associated with an impressive, albeit, short-lived response rate in the treatment of malignant melanoma. However, in CRC, BRAFi s have not proved efficacious as single agents [40]. Mechanisms of resistance seem to differ by tumor type; in melanoma the resistance mechanism includes upregulation of the MAPK pathway through mutations allegra mcevedy leon recipes for pork Costa allegra incendio vancouverMEK, and BRAF alternate splicing [41]. In CRC, primary resistance seems to be related to upregulation of the EGF receptor and the MAPK pathway [42].

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