1、BRAF V-Raf B1 (v-raf murine sarcoma viral oncogene homolog B, BRAF) - , (mitogen-activated protein kinase, MAPK) , , BRAF ; BRAF ; ; micRNA; , , 2015 , , , , , : 0 (CRC) , , CRC , 1 CRC , , CRC , , CRC , BRAF , , RAS/RAF/MAPK , 1 BRAF MAPK 1983 RAF , RAF , :ARAF, CRAF BRAF ( RAF1) BRAF 7q34 , - , BR
2、AF 90% 15 1799 , 600 , BRAFv600e 2 10% CRC BRAFV600E, V600E BRAF , BRAF 138 , 3 CRC BRAF , BRAF MAPK , MAPK , , 4 , , (RTK) , , ( RAS-RAF-MEK1/2-ERK1/2) , , , , BRAF V600E , 5 2 BRAF mic RNA mic RNA 18-25 RNA , 22nt RNA, RNA 3 , / m RNA RNA, CRC :MAPK Wnt , 6 mic RNA CRC 7 Wang 8 BRAF mir-378-5p , C
3、RC BRAF mi R-378-5p , , mi R-378-5p CRC BRAF Nosho 9 mi R-31 CRC BRAF , mi R-31 mi R-21 - , mic RNA 10; mic RNA, mi R-92a CRC 11, mi R-17-3p mi R-29a 12; , mi R-17-92 mir-135 13 mic RNA , BRAF , CRC 3 BRAF 3.1 BRAF , , (CIN) , 80-85% CRC CIN , KRAS BRAF APC P53 , - Cp G (CIMP) , - , BRAFV600E , MLH1
4、 , (MMR) , (MSI) 14 15-20% CRC MSI , (HNPCC Lynch ) 90% Lynch MSI , 15% MSI, Cp G BRAF (V600E) BRAF MSI-HCRC , , Lynch , MSI, BRAF CRC , Lynch BRAFV600E MLH1 (d MMR) Lynch 15 , , (CMS) :CMS1 (MSIImmune) , , , BRAF , ;CMS2 (Canonical) : , , WNT MYC ;CMS3 (Metabolic) : , ; CMS4 (Mesenchymal) , TGF- ,
5、16 BRAFV600E d MMR CRC ( CMS1) , , 3.2 BRAF BRAF (60 ) 17, I II 55 BRAF 18 Cremolini BRAF 594 596 BRAFV600E , BRAF 594 596 19 Jones , 1014 m CRC 137 BRAF , 29 V600E , , BRAFV600E 20 BRAF MSI-H 21-22 BRAFV600E m CRC 23, (PFS) (OS) 2.5 1 24-25 4 BRAF , CRC (EGF) (Cetuximab, Panitumumab, ) (VEGF) (beva
6、cizumab, ) BRAF , EGFR , BRAFV600E , EGFR 26 , BRAF BRAF , :I Dabrafenib Vemurafenib Dabrafenib , BRAF ATP , , BRAFV600E II Sorafenib, , BRAF27 CRAF, VEGFR-1 VEGFR-3 , , BRAF m CRC Vemurafenib EGFR , 28 BGB-283 Raf /EGFR , BRAFV600E EGFR / BGB-283 , MAPK BRAF 29 BRAF encorafenib (LGX818) , RAF , vem
7、urafenib dabarfenib 1b 54 BRAF m CRC , encorafenib encorafenib alpelisib ( ) , encorafenib 30 , BRAF EGFR , P13K MEK1/2 , 31 BRAF 32: (1) BRAFV600E MAPK ; (2) MAPK ERK DUSP (MAPK ) ; (3) micro RNA , mi R-579-3P BRAF MEK 33 , BRAF BRAF , , BRAF , , 5 BRAFV600E CRC , CRC , CRC , , BRAFV600E , BRAF , C
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