{"id":82329,"date":"2019-03-26T00:00:50","date_gmt":"2019-04-11T06:59:53","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/82329\/"},"modified":"2019-04-11T14:59:55","modified_gmt":"2019-04-11T06:59:55","slug":"9a1002d9da","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/82329\/","title":{"rendered":"\u9776\u5411RAF-MEK\u901a\u8def\u4e2d\u7684\u7a81\u53d8"},"content":{"rendered":"<div class=\"bpp-post-content\">\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<p style=\"text-align: center;width:10%;\" >\n<section style=\"margin-top: -20px;border-style: solid;border-width: 2px;border-color: #eaa67d;border-radius: 8px;padding: 15px;background-color: #ffffec;box-sizing: border-box;\">\n<section style=\"padding:5px 5px;border-bottom:solid;border-width:2px;border-color:#eaa67d;\">\n<p><span style=\"font-size: 15px;\">MAPK\u901a\u8def\u662f\u764c\u75c7\u4e2d\u6700\u5e38\u89c1\u7684\u7a81\u53d8\u81f4\u764c\u9014\u5f84\u4e4b\u4e00\u3002\u5c3d\u7ba1RAS\u7a81\u53d8\u5728MAPK\u901a\u8def\u6539\u53d8\u4e2d\u6700\u5e38\u89c1\uff0c\u4f46\u662f\u76f8\u5bf9\u6765\u8bf4\u7a81\u53d8\u8f83\u4e0d\u9891\u7e41\u7684\u901a\u8def\u4e0b\u6e38\u57fa\u56e0\uff08\u5305\u62ecRAF\u548cMEK\u57fa\u56e0\uff09\uff0c\u66f4\u6709\u5e0c\u671b\u5e26\u6765\u5408\u9002\u7684\u6cbb\u7597\u9776\u70b9\u3002\u9664\u9488\u5bf9BRAF V600\u7a81\u53d8\u5df2\u6709\u83b7\u6279\u7684\u6cbb\u7597\u65b9\u6848\u4ee5\u5916\uff0c RAF\u548cMEK\u7684\u5176\u5b83\u57fa\u56e0\u7a81\u53d8\u4e5f\u53ef\u80fd\u4f1a\u764c\u75c7\u6cbb\u7597\u63d0\u4f9b\u7f55\u89c1\u4f46\u66f4\u52a0\u5bb9\u6613\u63a7\u5236\u7684\u9776\u6807\u3002\u7136\u800c\uff0c\u8fd1\u671f\u7684\u7814\u7a76\u5df2\u7ecf\u9610\u660e\u4e86MAPK\u4fe1\u53f7\u901a\u8def\u7684\u590d\u6742\u6027\uff0c\u800c\u4e14\u8fd9\u4e9b\u57fa\u56e0\u7684\u5404\u79cd\u7a81\u53d8\u4f1a\u4f7f\u76f8\u5e94\u7684\u86cb\u767d\u4ea7\u751f\u622a\u7136\u4e0d\u540c\u7684\u5c5e\u6027\u3002\u6df1\u5ea6\u63a2\u7d22RAF\u548cMEK\u6fc0\u9176\u7684\u7279\u5b9a\u6539\u53d8\uff0c\u5bf9\u5f00\u53d1\u9488\u5bf9\u8fd9\u4e9b\u9776\u70b9\u7684\u6709\u6548\u6cbb\u7597\u7b56\u7565\u81f3\u5173\u91cd\u8981\u3002<\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">Ras\/Raf\/MEK\/ERK\u4fe1\u53f7\u7ea7\u8054\u901a\u8def\u662f\u4e00\u6761\u53ef\u88ab\u5e7f\u6cdb\u6fc0\u6d3b\u7684\u6709\u4e1d\u5206\u88c2\u539f\u6d3b\u5316\u86cb\u767d\u6fc0\u9176\uff08mitogen-activated protein kinase\uff0cMAPK\uff09\u901a\u8def\uff0c\u5b83\u80fd\u5c06\u7ec6\u80de\u5916\u4fe1\u53f7\u4f20\u9012\u5165\u7ec6\u80de\u6838\u5185\uff0c\u5f15\u8d77\u7ec6\u80de\u5185\u7279\u5f02\u86cb\u767d\u7684\u8868\u8fbe\u8c31\u53d8\u5316\uff0c\u4ece\u800c\u5f71\u54cd\u7ec6\u80de\u547d\u8fd0\u3002MAPK\u4fe1\u53f7\u8f6c\u5bfc\u662f\u4ee5\u4e09\u7ea7\u6fc0\u9176\u7ea7\u8054\u7684\u65b9\u5f0f\u8fdb\u884c\u7684\uff0c\u9996\u5148MAPKKK\u53d7\u6709\u4e1d\u5206\u88c2\u539f\u523a\u6fc0\u78f7\u9178\u5316\u800c\u6fc0\u6d3b\uff0c\u5728\u6b64\u57fa\u7840\u4e0aMAPKKK \u8f6c\u800c\u78f7\u9178\u5316\u6fc0\u6d3bMAPKK\uff0c\u6700\u540e\u7531MAPKK \u78f7\u9178\u5316MAPK\uff0c\u4f7f\u5176\u6d3b\u5316\u8fdb\u800c\u8f6c\u5165\u6838\u5185\uff08\u56fe1\uff09\u3002MAPK\u4fe1\u53f7\u901a\u8def\u4e0e\u8bb8\u591a\u91cd\u8981\u7684\u7ec6\u80de\u8fc7\u7a0b\u5bc6\u5207\u76f8\u5173\uff0c\u8be5\u901a\u8def\u5931\u8c03\u4f1a\u5bfc\u81f4\u4e0d\u53d7\u63a7\u5236\u7684\u7ec6\u80de\u589e\u6b96\u3001\u5b58\u6d3b\u548c\u53bb\u5206\u5316\u3002\u5728\u5927\u591a\u6570\u764c\u75c7\u4e2d\uff0cMAPK\u901a\u8def\u5b58\u5728\u5f02\u5e38\u6fc0\u6d3b\u3002RAS\u86cb\u767d\uff08KRAS\u3001NRAS\u3001HRAS\uff09\u5c5eGTPases\uff08\u9e1f\u560c\u5464\u4e09\u78f7\u9178\u9176\uff09\u86cb\u767d\u8d85\u5bb6\u65cf\u4e00\u5458\uff0c\u53ef\u4f5c\u4e3a\u5206\u5b50\u5f00\u5173\u6fc0\u52a8\u4e0b\u6e38RAF \u86cb\u767d\u6fc0\u9176\uff08BRAF\u3001CRAF\u3001ARAF\uff09\u3002RAF \u86cb\u767d\u6fc0\u9176\u4e2d\u91cd\u8981\u7684\u5e95\u7269\u662fMEK\u6fc0\u9176\uff08MEK1\u3001MEK2\uff09\u3002\u800cMEK\u6fc0\u9176\u53ea\u6709\u4e00\u4e2a\u4e3b\u8981\u7684\u7ec6\u80de\u5916\u4fe1\u53f7\u8c03\u8282\u6fc0\u9176ERK\u3002MAPK\u901a\u8def\u4e2d\u57fa\u56e0\u7ec4\u6539\u53d8\u7684\u9891\u7387\u968f\u7740\u5176\u8fdb\u4e00\u6b65\u5411\u4e0b\u6e38\u79fb\u52a8\u800c\u964d\u4f4e\uff1a\u5728\u4eba\u7c7b\u80bf\u7624\u4e2d\uff0cRAS\u7a81\u53d8\u53d1\u751f\u7387\u4e3a22%\uff0cBRAF\u7a81\u53d8\u53d1\u751f\u7387\u4e3a7%\uff0cMEK\u7a81\u53d8\u53d1\u751f\u5728&lt;1%\u7684\u75c5\u4f8b\u4e2d\uff0c\u800cERK\u7a81\u53d8\u975e\u5e38\u7f55\u89c1\u3002\u5c3d\u7ba1RAS\u7a81\u53d8\u5728MAPK\u901a\u8def\u6539\u53d8\u4e2d\u6700\u5e38\u89c1\uff0c\u4f46\u662f\u672c\u6587\u5c06\u7740\u91cd\u4ecb\u7ecdRAF\u548cMEK\u57fa\u56e0\u7a81\u53d8\uff0c\u671f\u671b\u5bfb\u627e\u66f4\u6709\u5e0c\u671b\u6cbb\u7597\u65b9\u6cd5\u3002<\/span><\/p>\n<p style=\"text-align: center;\"><img class=\"rich_pages\"          style=\"width: 100%;height: auto;\" src=\"http:\/\/www.05921.net\/wp-content\/uploads\/2019\/04\/4-1554965994.jpeg\" alt=\"\u9776\u5411RAF-MEK\u901a\u8def\u4e2d\u7684\u7a81\u53d8\" title=\"\u9776\u5411RAF-MEK\u901a\u8def\u4e2d\u7684\u7a81\u53d8\"  \/><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: 15px;\">\u56fe1\uff1aRas\/Raf\/MEK\/ERK\u4fe1\u53f7\u4f20\u5bfc<\/span><\/p>\n<p style=\"text-align: center;\"><br  \/><\/p>\n<section class=\"_editor\">\n<section style=\"text-align: center;margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"text-align: center;\">\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;font-size: 16px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"font-size: 17px;color: #ffffff;\"><strong>RAF\u7a81\u53d8<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><br  \/><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p style=\"text-indent: 2em;\"><br  \/><\/p>\n<p style=\"text-indent: 2em;\">BRAF\u662fMAPK\u4fe1\u53f7\u901a\u8def\u4e2dRAS\u86cb\u767d\u4e0b\u6e38\u6700\u5e38\u89c1\u7684\u7a81\u53d8\u57fa\u56e0\uff0c\u57287%~10%\u7684\u764c\u75c7\u4e2d\u4f1a\u53d1\u751f\u7a81\u53d8\u3002\u70b9\u7a81\u53d8\u662fBRAF\u4e2d\u6700\u5e38\u89c1\u7684\u7a81\u53d8\u6a21\u5f0f\uff0c\u4f46\u5728\u67d0\u4e9b\u764c\u75c7\u4e2d\u4e5f\u53ef\u4ee5\u89c2\u5bdf\u5230\u57fa\u56e0\u878d\u5408\u548c\u6846\u5185\u7f3a\u5931\u3002\u6700\u8fd1\u7684\u7814\u7a76\u8868\u660e\uff0cBRAF\u7684\u4e0d\u540c\u5f62\u5f0f\u7684\u7a81\u53d8\u53ef\u4ee5\u4ea7\u751f\u4e00\u7cfb\u5217\u4e0d\u540c\u7684\u529f\u80fd\u5f02\u5e38\u3002\u901a\u5e38\u60c5\u51b5\u4e0b\uff0cRAF\u86cb\u767d\u9700\u8981\u4e0eRAS\u76f8\u4e92\u4f5c\u7528\u624d\u80fd\u53d1\u751f\u4e8c\u805a\u5316\u5e76\u4e14\u5b8c\u6210\u968f\u540e\u7684\u6fc0\u6d3b\uff0c\u5176\u6838\u5fc3\u529f\u80fd\u7684\u5f02\u5e38\u53d8\u5316\u901a\u5e38\u662f\u7531\u57fa\u56e0\u7a81\u53d8\u6539\u53d8\u8fd9\u79cd\u76f8\u4e92\u4f5c\u7528\u800c\u9a71\u52a8\u7684\u3002\u6bcf\u79cd\u7279\u5b9a\u7684\u7a81\u53d8\u5982\u4f55\u5f71\u54cdRAF\u4e8c\u805a\u4f53\u7684\u5f62\u6210\u548c\u529f\u80fd\uff0c\u5bf9\u4e8e\u5bfb\u627e\u9776\u5411\u4e0d\u540c\u7684\u7a81\u53d8\u4f53\u6240\u9700\u7684\u4e0d\u540c\u6cbb\u7597\u7b56\u7565\u81f3\u5173\u91cd\u8981\u3002\u603b\u4e4b\uff0cBRAF\u7a81\u53d8\u53ef\u5206\u4e3a\u4e09\u7c7b\uff0c\u5176\u4e2d\u2160\u7c7b\u548c\u2161\u7c7b\u7a81\u53d8\u4f53\u6784\u6210\u4e86\u201c\u6d3b\u5316\u5242\uff08activators\uff09\u201d\uff0c\u2162\u7c7b\u7a81\u53d8\u4f53\u8868\u73b0\u4e3a\u201c\u589e\u5f3a\u5242\uff08amplifiers\uff09\u201d\uff08\u56fe2\uff09\u3002<\/p>\n<p style=\"text-align: center;\"><img class=\"rich_pages\"          style=\"width: 100%;height: auto;\" src=\"http:\/\/www.05921.net\/wp-content\/uploads\/2019\/04\/9-1554965994.jpeg\" alt=\"\u9776\u5411RAF-MEK\u901a\u8def\u4e2d\u7684\u7a81\u53d8\" title=\"\u9776\u5411RAF-MEK\u901a\u8def\u4e2d\u7684\u7a81\u53d8\"  \/><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: 15px;\">\u56fe2\uff1aBRAF\u7a81\u53d8\u7684\u5206\u7c7b<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: 15px;\"><br  \/><\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u2160\u7c7bBRAF\u7a81\u53d8\u4ea7\u751fBRAF\u5355\u4f53\u4fe1\u53f7\uff0c\u4e0eRAS\u6fc0\u6d3b\u65e0\u5173\u3002\u5b83\u4eec\u53ef\u4ee5\u5bfc\u81f4\u9ad8\u6c34\u5e73\u7684ERK\u6fc0\u6d3b\uff0c\u4ece\u800c\u5bfc\u81f4\u4e0a\u6e38\u4fe1\u53f7\u7684\u8d1f\u53cd\u9988\u6291\u5236\u3002\u56e0\u6b64\u5728\u2160\u7c7bBRAF\u7a81\u53d8\u7684\u80bf\u7624\u4e2d\uff0cRAS-GTP\u6c34\u5e73\u8f83\u4f4e\u3002\u2161\u7c7bBRAF\u7a81\u53d8\u4ea7\u751f\u4e0eRAS\u65e0\u5173\u7684\u7a81\u53d8BRAF\u4e8c\u805a\u4f53\u3002\u5b83\u4eec\u53ef\u4ee5\u5f3a\u70c8\u6fc0\u6d3bERK\uff0c\u5bfc\u81f4\u4e0a\u6e38\u4fe1\u53f7\u7684\u8d1f\u53cd\u9988\u6291\u5236\u4ee5\u53ca\u4f4e\u6c34\u5e73\u7684RAS-GTP\u3002\u2162\u7c7bBRAF\u7a81\u53d8\u5bfc\u81f4\u5176\u5bf9RAS\u548cCRAF\u7ed3\u5408\u80fd\u529b\u7684\u589e\u5f3a\uff0c\u751f\u6210\u7a81\u53d8\u578bBRAF\u548c\u91ce\u751f\u578bCRAF\u7684\u4e8c\u805a\u4f53\u3002\u5b83\u4eec\u4f1a\u653e\u5927RAS\u7684\u4e0b\u6e38\u4fe1\u53f7\uff0c\u4e3b\u8981\u901a\u8fc7\u57fa\u56e0\u7a81\u53d8\uff08RAS\u7a81\u53d8\u6216NF1\u7f3a\u5931\uff09\u6216\u8005RTK\uff08\u53d7\u4f53\u916a\u6c28\u9178\u6fc0\u9176\uff09\u7b49\u4e0a\u6e38\u4fe1\u53f7\u6fc0\u6d3b\u6765\u589e\u52a0ERK\u4fe1\u53f7\u3002\u5177\u6709\u8fd9\u4e9b\u7a81\u53d8\u7684\u80bf\u7624\u8868\u73b0\u51fa\u8f83\u9ad8\u7684RAS-GTP\u6c34\u5e73\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><br  \/><\/span><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;font-size: 16px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"font-size: 17px;color: #ffffff;\"><strong>MEK\u7a81\u53d8<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><\/span><br  \/><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u4e0eRAS\u548cBRAF\u7684\u70ed\u70b9\u7a81\u53d8\u4e0d\u540c\uff0c\u5f71\u54cdMEK1\u548cMEK2\u7684\u7a81\u53d8\u53ef\u4ee5\u5206\u522b\u53d1\u751fMAP2K1\u6216\u8005MAP2K2\u57fa\u56e0\u4e0a\u3002\u8fd1\u671f\uff0c\u6709\u7814\u7a76\u4eba\u5458\u5bf9\u7ecf\u5e38\u53d1\u751f\u7684MEK1\u7a81\u53d8\u4f53\u7684\u529f\u80fd\u8fdb\u884c\u4e86\u9610\u660e\uff0c\u4ed6\u4eec\u8ba4\u4e3a\u8fd9\u4e9b\u7a81\u53d8\u4f53\u53ef\u6839\u636e\u529f\u80fd\u5206\u4e3a\u4e09\u7c7b\uff1aRAF-\u975e\u4f9d\u8d56\u578b\u3001RAF-\u8c03\u8282\u578b\u4ee5\u53caRAF-\u4f9d\u8d56\u578b\uff08\u56fe3\uff09\u3002<\/span><\/p>\n<p style=\"text-align: center;\"><img class=\"rich_pages\"       style=\"\" src=\"http:\/\/www.05921.net\/wp-content\/uploads\/2019\/04\/10-1554965994.jpeg\" alt=\"\u9776\u5411RAF-MEK\u901a\u8def\u4e2d\u7684\u7a81\u53d8\" title=\"\u9776\u5411RAF-MEK\u901a\u8def\u4e2d\u7684\u7a81\u53d8\"  \/><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: 15px;\">\u56fe3\uff1aMEK\u7a81\u53d8\u7684\u529f\u80fd\u5206\u7c7b<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><br  \/><\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u4e0a\u56fe\u5c55\u793a\u4e86\u751f\u7406\u6027MAPK\u4fe1\u53f7\u901a\u8def\uff08\u5de6\uff09\u4ee5\u53caMEK\u7a81\u53d8\u7ec6\u80de\u7684\u4fe1\u53f7\u901a\u8def\u3002RAF\u975e\u4f9d\u8d56\u578b\u7684MEK\u7a81\u53d8\u5f3a\u70c8\u6fc0\u6d3bERK\u5e76\u8bf1\u5bfc\u4e0a\u6e38\u4fe1\u53f7\u7684\u8d1f\u53cd\u9988\u8c03\u8282\u3002\u8fd9\u4e9b\u7a81\u53d8\u53ef\u4ee5\u81ea\u78f7\u9178\u5316MEK\u4e0a\u7684\u8c03\u8282\u4f4d\u70b9S218\u548cS222\u3002RAF\u8c03\u8282\u578b\u7684MEK\u7a81\u53d8\u663e\u793a\u51fa\u72ec\u7acb\u7684\u6fc0\u9176\u6d3b\u6027\uff0c\u4f46\u5728\u6d3b\u5316\u7684RAF\u5b58\u5728\u7684\u60c5\u51b5\u4e0b\uff0c\u8fd9\u79cd\u6d3b\u6027\u4f1a\u8fdb\u4e00\u6b65\u589e\u5f3a\uff0c\u5f3a\u5316\u6765\u81eaRAF\u7684\u4fe1\u53f7\u3002\u5b83\u4eec\u6fc0\u6d3bERK\u4fe1\u53f7\u7684\u7a0b\u5ea6\u65e0\u6cd5\u4e0eRAF\u975e\u4f9d\u8d56\u578b\u7684MEK\u7a81\u53d8\u76f8\u6bd4\uff0c\u56e0\u6b64\u5bf9\u4e0a\u6e38\u4fe1\u53f7\u7684\u8d1f\u53cd\u9988\u6291\u5236\u8c03\u8282\u8981\u6e29\u548c\u8bb8\u591a\u3002RAF\u4f9d\u8d56\u578b\u7684MEK\u7a81\u53d8\u53ea\u5728\u6fc0\u6d3bRAF\u7684\u60c5\u51b5\u4e0b\u589e\u52a0ERK\u7684\u6fc0\u6d3b\uff1b\u5b83\u4eec\u4e0eRAF\u7ed3\u5408\u66f4\u7d27\u5bc6\uff0c\u4ece\u800c\u589e\u52a0ERK\u6fc0\u6d3b\u3002\u5b83\u4eec\u6e29\u548c\u5730\u6fc0\u6d3bERK\uff0c\u5e76\u5bfc\u81f4\u6700\u5c0f\u7684\u4e0a\u6e38\u4fe1\u53f7\u53cd\u9988\u6291\u5236\uff0c\u901a\u5e38\u4e0e\u4e0a\u6e38\u7684\u6fc0\u6d3b\u7a81\u53d8\u5171\u540c\u53d1\u751f\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><br  \/><\/span><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;font-size: 16px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"font-size: 17px;color: #ffffff;\"><strong>MAPK\u901a\u8def\u6291\u5236\u5242<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><\/span><br  \/><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;font-size: 16px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"font-size: 17px;color: #ffffff;\"><strong>RAF\u6291\u5236\u5242<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><br  \/><\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u76ee\u524d\u6279\u51c6\u7684RAF\u6291\u5236\u5242\u90fd\u662f\u9009\u62e9\u6027\u6291\u5236RAF\u5355\u4f53\uff08\u5982\u2160\u7c7b\uff0cBRAFV600\u7a81\u53d8\uff09\u3002\u5c3d\u7ba1\u8fd9\u4e9b\u6291\u5236\u5242\uff0c\u5982vemurafenib\u3001dabrafenib\u548cencorafenib\uff0c\u901a\u5e38\u88ab\u79f0\u4e3a\u201cBRAF\u6291\u5236\u5242\u201d\uff0c\u4f46\u5b9e\u9645\u4e0a\u5b83\u4eec\u5bf9BRAF\u6ca1\u6709\u9009\u62e9\u6027\uff0c\u5e76\u4e14\u80fd\u591f\u4ee5\u7c7b\u4f3c\u7684\u6548\u529b\u6291\u5236ARAF\u548cCRAF\u3002\u8fd9\u4e9b\u6291\u5236\u5242\u5728BRAFV600\u7a81\u53d8\u764c\u75c7\u4e2d\u7684\u4f5c\u7528\u662f\u901a\u8fc7\u6291\u5236BRAF\u7a81\u53d8\u5355\u4f53\u6765\u5b9e\u73b0\u3002\u4e8b\u5b9e\u4e0a\uff0c\u8fd9\u4e9b\u6291\u5236\u5242\u5728\u7f3a\u4e4fBRAFV600\u7a81\u53d8\u7684\u7ec6\u80de\u4e2d\u7684\u4f5c\u7528\u662f\u590d\u6742\u7684\u3002RAF\u6291\u5236\u5242\u7ed3\u5408\u81f3\u4e8c\u805a\u4f53\u4e2d\u7684\u4e00\u4e2aRAF\u539f\u805a\u4f53\u4f1a\u53cd\u5f0f\u6fc0\u6d3b\u53e6\u4e00\u4e2a\u539f\u805a\u4f53\uff0c\u540c\u65f6\u964d\u4f4e\u836f\u7269\u5bf9\u53e6\u4e00\u4e2a\u539f\u805a\u4f53\u7684\u4eb2\u548c\u529b\u3002\u8fd9\u4e9b\u6291\u5236\u5242\u7ed3\u5408\u03b1C\u87ba\u65cb\u7684\u975e\u6d3b\u6027\u6784\u8c61\uff1b\u836f\u7269\u7ed3\u5408\u7a33\u5b9a\u4e86\u7b2c\u4e00\u4e2a\u539f\u805a\u4f53\u7684\u975e\u6d3b\u6027\u6784\u8c61\uff0c\u5e76\u4e14\u5c06\u53e6\u4e00\u4e2a\u539f\u805a\u4f53\u8f6c\u53d8\u6210\u6d3b\u6027\u6784\u8c61\uff0c\u8fd9\u6837\u5c31\u4f1a\u56e0\u4e3a\u4f4d\u963b\u7684\u5173\u7cfb\u65e0\u6cd5\u4e0e\u836f\u7269\u7ed3\u5408\u3002\u56e0\u6b64\uff0c\u6291\u5236\u5242\u4e0eRAF\u4e8c\u805a\u4f53\u4e2d\u7684\u4e00\u4e2a\u539f\u805a\u4f53\u7ed3\u5408\uff0c\u5b9e\u9645\u4e0a\u4f1a\u901a\u8fc7\u53e6\u4e00\u4e2a\u539f\u805a\u4f53\u7684\u53cd\u5f0f\u6fc0\u6d3b\u800c\u5bfc\u81f4RAF\u4fe1\u53f7\u7684\u7279\u6b8a\u6fc0\u6d3b\u4f5c\u7528\u3002\u8fd9\u5c31\u9700\u8981\u66f4\u9ad8\u5242\u91cf\u7684RAF\u6291\u5236\u5242\u6765\u514b\u670d\u8fd9\u79cd\u8d1f\u534f\u540c\u6548\u5e94\uff0c\u5e76\u4e14\u7ed3\u5408\u4e8c\u805a\u4f53\u4e2d\u7684\u4e24\u4e2a\u539f\u805a\u4f53\u6765\u5b8c\u5168\u7684\u963b\u65adRAF\u4e8c\u805a\u4f53\u4fe1\u53f7\u4f20\u5bfc\uff0c\u800c\u8fd9\u79cd\u9ad8\u5242\u91cf\u65e0\u6cd5\u5728\u75c5\u4eba\u4f53\u5185\u5b9e\u73b0\u3002\u56e0\u6b64\uff0c\u8fd9\u4e9b\u836f\u7269\u5bf9RAF\u4fe1\u53f7\u4e3a\u4e8c\u805a\u4f53\u7684\u80bf\u7624\u65e0\u6548\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u65b0\u578bRAF\u6291\u5236\u5242\u7684\u9009\u62e9\u6027\u4e0eRAF\u5355\u4f53\u6291\u5236\u5242\u4e0d\u540c\u3002\u6240\u6709RAF\u6291\u5236\u5242\u5bf9BRAFV600E\u5747\u8868\u73b0\u51fa\u4e00\u5b9a\u7a0b\u5ea6\u7684\u4f18\u5148\u6291\u5236\u4f5c\u7528\uff0c\u56e0\u4e3a\u4e0e\u91ce\u751f\u578bBRAF\u76f8\u6bd4\uff0cBRAFV600E\u5177\u6709\u8f83\u5f31\u7684ATP\u7ed3\u5408\u4eb2\u548c\u529b\u3002\u65b0\u578b\u7684RAF\u6291\u5236\u5242\u88ab\u79f0\u4e3a\u201cRAF\u4e8c\u805a\u4f53\u6291\u5236\u5242\u201d\uff0c\u5b83\u4eec\u4ee5\u7b49\u5242\u91cf\u7ed3\u5408RAF\u4e8c\u805a\u4f53\u4e2d\u7684\u4f4d\u70b9\u3002\u8fd9\u4e9b\u836f\u7269\u5e94\u8be5\u6709\u76f8\u5e94\u7684\u6cbb\u7597\u6307\u6570\uff0c\u56e0\u4e3a\u5b83\u4eec\u6291\u5236\u7a81\u53d8\u7684RAF\u4e8c\u805a\u4f53\u548c\u5355\u4f53\u6bd4\u6291\u5236\u91ce\u751f\u578b\u4e8c\u805a\u4f53\u66f4\u6709\u6548\u529b\uff0c\u56e0\u6b64\u5728\u6b63\u5e38\u7ec6\u80de\u4e2d\u4e0d\u4f1a\u540c\u6837\u7a0b\u5ea6\u5730\u6291\u5236MAPK\u4fe1\u53f7\u3002\u4ece\u673a\u5236\u4e0a\u8bb2\uff0c\u8fd9\u4e9bRAF\u6291\u5236\u5242\u6709\u671b\u6291\u5236\u5177\u6709RAF\u7a81\u53d8\u4e8c\u805a\u4f53\u7684\u80bf\u7624\uff0c\u5305\u62ec\u975e-V600 BRAF\u6fc0\u6d3b\u7a81\u53d8\u548cBRAF V600\u80bf\u7624\uff0c\u8fd9\u4e9b\u80bf\u7624\u901a\u8fc7\u57fa\u56e0\u7ec4\u6539\u53d8\uff08\u5982RAS\u7a81\u53d8\/\u6269\u589e\u3001BRAFV600E\u6269\u589e\u6216BRAF\u5185\u542b\u5b50\u7f3a\u5931\u6216\u526a\u63a5\u53d8\u5f02\uff0c\u8fd9\u4e9b\u4f1a\u5bfc\u81f4BRAFV600\u4e8c\u805a\u5316\uff09\u5bf9RAF\u6291\u5236\u5242\u4ea7\u751f\u8010\u836f\u6027\u3002\u65b0\u4e00\u4ee3\u7684RAF\u6291\u5236\u5242\uff08\u5982PLX8394\uff09\u901a\u5e38\u88ab\u79f0\u4e3a\u201c\u65ad\u5f00\u5242\u201d\uff0c\u76ee\u524d\u5728\u4e34\u5e8a\u2160\u671f\u7814\u53d1\u9636\u6bb5\u3002\u8fd9\u4e9b\u836f\u7269\u53ef\u4ee5\u901a\u8fc7\u5e72\u6270\u542b\u6709BRAF\u7684\u4e8c\u805a\u4f53\uff08\u5305\u62ecBRAF-BRAF\u540c\u6e90\u4e8c\u805a\u4f53\u548cBRAF\u5f02\u6e90\u4e8c\u805a\u4f53\uff09\u6765\u6291\u5236\u4fe1\u53f7\u4f20\u5bfc\u3002\u8fd9\u4e9b\u836f\u7269\u5bf9CRAF\u540c\u6e90\u4e8c\u805a\u4f53\u548c\u542b\u6709ARAF\u4e8c\u805a\u4f53\u6ca1\u6709\u6548\u679c\uff0c\u53ef\u80fd\u662f\u7531\u4e8e\u4f4d\u4e8eRAF\u6fc0\u9176N\u7aef\u7684\u6c28\u57fa\u9178\u6b8b\u57fa\u4f7f\u8fd9\u4e9b\u4e8c\u805a\u4f53\u7a33\u5b9a\u6027\u589e\u5f3a\u3002RAF\u4e8c\u805a\u4f53\u6291\u5236\u5242\u5728\u4e0d\u540c\u7684RAF\u4e9a\u578b\u4e4b\u95f4\u9009\u62e9\u6027\u8f83\u4f4e\uff0c\u5373\u4f7f\u5728\u4e0a\u6e38RAS\u6d3b\u5316\u8f83\u5f3a\u7684\u7ec6\u80de\u4e2d\u4e5f\u53ef\u4ee5\u6291\u5236RAF\u4fe1\u53f7\u3002\u7531\u4e8e\u8fd9\u4e9b\u6291\u5236\u5242\u5728\u6b63\u5e38\u7ec6\u80de\u548c\u80bf\u7624\u7ec6\u80de\u4e2d\u90fd\u53ef\u4ee5\u6291\u5236MAPK\u4fe1\u53f7\uff0c\u8fd9\u4e9b\u836f\u7269\u7684\u6cbb\u7597\u7a97\u53e3\u53ef\u80fd\u6bd4\u201cRAF\u4e8c\u805a\u4f53\u65ad\u5f00\u5242\u201d\u66f4\u7a84\u3002\u5728\u4e8c\u805a\u4f53\u6291\u5236\u5242LY3009120\u7684\u2160\u671f\u8bd5\u9a8c\u4e2d\uff0c\u5242\u91cf\u589e\u52a0\u6709\u9650\uff0c\u8be5\u5316\u5408\u7269\u7684\u6700\u5927\u8010\u53d7\u5242\u91cf\u5bf9\u80bf\u7624ERK\u78f7\u9178\u5316\u6c34\u5e73\u548cERK\u9776\u57fa\u56e0\u8868\u8fbe\u7684\u5f71\u54cd\u5f88\u5c0f\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><br  \/><\/span><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;font-size: 16px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"font-size: 17px;color: #ffffff;\"><strong>MEK\u6291\u5236\u5242<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p style=\"text-indent: 2em;\"><br  \/><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u8bb8\u591aMEK\u6291\u5236\u5242\uff08\u4f8b\u5982selumetinib\u548c3\u4e2a\u5df2\u83b7FDA\u6279\u51c6\u7684trametinib\u3001cobimetinib\u548c binimetinib\uff09\u90fd\u662f\u53d8\u6784\u6fc0\u9176\u6291\u5236\u5242\u3002\u8fd9\u4e9b\u5316\u5408\u7269\u4e0eMEK\u50ac\u5316\u4f4d\u70b9\u9644\u8fd1\u7684\u53d8\u6784\u53e3\u888b\u7ed3\u5408\uff0c\u5bfc\u81f4\u6784\u578b\u6539\u53d8\uff0c\u4ece\u800c\u6291\u5236MEK\u6fc0\u9176\u6d3b\u6027\u3002\u5177\u4f53\u6765\u8bf4\uff0c\u836f\u7269\u7ed3\u5408\u4f1a\u4f7fMEK\u91c7\u7528\u201c\u5c01\u95ed\u201d\u6784\u8c61\uff0c\u5e76\u5bfc\u81f4\u4e00\u7cfb\u5217\u6784\u8c61\u6539\u53d8\uff0c\u8fd9\u4e9b\u6784\u8c61\u53d8\u5316\u5c06\u9ad8\u5ea6\u4fdd\u5b88\u7684\u8c37\u6c28\u9178\u6b8b\u57fa\uff08Glu114\uff09\u4ece\u6d3b\u6027\u90e8\u4f4d\u8f6c\u79fb\u5f00\uff0c\u4ece\u800c\u4f7f\u5176\u65e0\u6cd5\u4e0e\u4fdd\u5b88\u7684\u50ac\u5316\u8d56\u6c28\u9178\u6b8b\u57fa\uff08Lys97\uff09\u5f62\u6210\u4e34\u754c\u79bb\u5b50\u5bf9\u3002MEK\u53d8\u6784\u6291\u5236\u5242\u6709\u8bb8\u591a\u786e\u5b9a\u7684\u4f18\u52bf\uff0c\u56e0\u4e3a\u5b83\u4eec\u4e0eMEK\u4e0a\u72ec\u7279\u7684\u53d8\u6784\u53e3\u888b\u7ed3\u5408\uff0c\u800c\u4e0d\u662f\u4e0e\u50ac\u5316\u4f4d\u70b9\uff08\u4e0e\u5176\u5b83\u6fc0\u9176\u5177\u6709\u8f83\u9ad8\u540c\u6e90\u6027\uff09\u7ed3\u5408\uff0c\u8fd9\u4e9b\u6291\u5236\u5242\u5bf9MEK\u5177\u6709\u9ad8\u5ea6\u7279\u5f02\u6027\uff0c\u56e0\u6b64\u8f83\u5c11\u51fa\u73b0\u8131\u9776\u5f15\u8d77\u7684\u6bd2\u6027\u3002\u7136\u800c\uff0cMEK\u53d8\u6784\u6291\u5236\u5242\u4e5f\u6709\u5173\u952e\u7684\u5f31\u70b9\u3002\u5c24\u5176\u662f\uff0c\u5728\u4e0a\u6e38MAPK\u4fe1\u53f7\u589e\u52a0\u7684\u60c5\u51b5\u4e0b\uff0c\u8bb8\u591aMEK\u53d8\u6784\u6291\u5236\u5242\u6291\u5236MEK\u6fc0\u9176\u6d3b\u6027\u7684\u80fd\u529b\u4e0b\u964d\uff0c\u4ece\u800c\u5bfc\u81f4MEK\u6d3b\u5316\u589e\u52a0\u3002\u8fd9\u53ef\u80fd\u901a\u8fc7\u4e24\u79cd\u6f5c\u5728\u673a\u5236\u5171\u540c\u4f5c\u7528\u800c\u53d1\u751f\u3002\u9996\u5148\uff0c\u8bb8\u591aMEK\u6291\u5236\u5242\u4f18\u5148\u4e0eMEK\u7684\u975e\u6d3b\u6027\u5f62\u5f0f\u7ed3\u5408\uff0c\u5f53MEK\u5904\u4e8e\u78f7\u9178\u5316\u548c\u6d3b\u5316\u5f62\u5f0f\u65f6\uff0c\u4e0eMEK\u6291\u5236\u5242\u7ed3\u5408\u7684\u4eb2\u548c\u529b\u964d\u4f4e\u3002\u5982\u679c\u4e0a\u6e38\u4fe1\u53f7\u589e\u52a0\uff0c\u4f1a\u5bfc\u81f4MEK\u78f7\u9178\u5316\u548c\u6d3b\u5316\u6c34\u5e73\u589e\u52a0\uff0c\u6291\u5236\u5242\u4e0eMEK\u7ed3\u5408\u7684\u80fd\u529b\u5c31\u4f1a\u56e0\u6b64\u51cf\u5f31\u3002\u5176\u6b21\uff0c\u4e0a\u6e38MAPK\u4fe1\u53f7\u7684\u663e\u8457\u589e\u52a0\uff0c\u4f1a\u5bfc\u81f4\u6d3b\u5316\u7684MEK\u8fdc\u8fdc\u8d85\u51fa\u8bf1\u5bfc\u6700\u5927ERK\u6c34\u5e73\u6240\u9700\u7684\u5242\u91cf\u3002\u56e0\u6b64\uff0c\u9700\u8981\u76f8\u5bf9\u4e8e\u57fa\u7ebf\u6761\u4ef6\u66f4\u9ad8\u6d53\u5ea6\u7684\u6291\u5236\u5242\u6765\u6291\u5236MEK\u6c34\u5e73\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u6b63\u56e0\u4e3a\u5982\u6b64\uff0c\u8bb8\u591aMEK\u6291\u5236\u5242\u4ea7\u751f\u7684\u539f\u53d1\u548c\u7ee7\u53d1\uff08\u4f8b\u5982\u83b7\u5f97\u6027\uff09\u8010\u836f\u673a\u5236\u90fd\u6d89\u53ca\u5230MEK\u201c\u4e0a\u6e38\u201d\u4fe1\u53f7\u7684\u589e\u52a0\u3002\u8fd9\u4e0e\u5176\u5b83\u9776\u5411\u836f\u7269\u7684\u5178\u578b\u8010\u836f\u673a\u5236\u5f62\u6210\u9c9c\u660e\u5bf9\u6bd4\uff0c\u540e\u8005\u5f80\u5f80\u6d89\u53ca\u836f\u7269\u9776\u6807\u6216\u5176\u201c\u4e0b\u6e38\u201d\u4fe1\u53f7\u6c34\u5e73\u7684\u6539\u53d8\u3002MEK\u6291\u5236\u5242\u5bf9MAPK\u4fe1\u53f7\u81ea\u9002\u5e94\u53cd\u9988\u518d\u6fc0\u6d3b\u975e\u5e38\u654f\u611f\u3002\u5728\u8fd9\u79cd\u60c5\u51b5\u4e0b\uff0cMEK\u6291\u5236\u5242\u5bf9ERK\u78f7\u9178\u5316\u7684\u77ac\u65f6\u6291\u5236\uff0c\u5bfc\u81f4\u4e0a\u6e38MAPK\u901a\u8def\u7684\u8d1f\u53cd\u9988\u6291\u5236\u51cf\u5c11\uff0c\u4ece\u800c\u5bfc\u81f4RAS\u6fc0\u6d3b\u589e\u52a0\uff08\u901a\u5e38\u9700\u8981RTK\u7684\u53c2\u4e0e\uff09\uff0c\u6700\u7ec8\u589e\u52a0RAF\u4ecb\u5bfc\u7684MEK\u78f7\u9178\u5316\u3002\u56e0\u6b64\uff0c\u5728MEK\u6291\u5236\u5242\u6cbb\u7597\u540e\uff0c\u5c3d\u7ba1MEK\u6291\u5236\u5242\u6301\u7eed\u5b58\u5728\uff0c\u4f46\u968f\u7740\u65f6\u95f4\u7684\u63a8\u8fdf\uff0c\u4f9d\u7136\u4f1a\u89c2\u5bdf\u5230MEK\u78f7\u9178\u5316\u663e\u8457\u589e\u52a0\uff0c\u8fd9\u79cd\u53cd\u9988\u6700\u7ec8\u5bfc\u81f4ERK\u78f7\u9178\u5316\u589e\u52a0\u3002\u540c\u6837\uff0c\u4f7f\u7528RAF\u548cMEK\u6291\u5236\u5242\u8054\u7528\u6cbb\u7597BRAFV600\u7a81\u53d8\u764c\u75c7\u800c\u51fa\u73b0\u7684\u4e34\u5e8a\u83b7\u5f97\u6027\u8010\u836f\u6027\u4e2d\uff0c\u53ef\u4ee5\u89c2\u5bdf\u5230MAPK\u901a\u8def\u7684\u591a\u91cd\u4e0a\u6e38\u4fe1\u53f7\u7a81\u53d8\uff0c\u5305\u62ecKRAS\u548cNRAS\u7a81\u53d8\u3001BRAFV600\u7b49\u4f4d\u57fa\u56e0\u6269\u589e\u548cRTK\u6269\u589e\u3002\u8fd9\u90fd\u4f1a\u5bfc\u81f4MEK\u78f7\u9178\u5316\u548c\u6d3b\u5316\u589e\u52a0\uff0c\u5e76\u964d\u4f4eMEK\u6291\u5236\u5242\u7684\u7597\u6548\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u7136\u800c\uff0c\u4e0d\u540cMEK\u53d8\u6784\u6291\u5236\u5242\u4e4b\u95f4\u4e5f\u5b58\u5728\u5173\u952e\u6027\u5dee\u5f02\uff0c\u4e00\u4e9b\u6291\u5236\u5242\u53ef\u4ee5\u5f71\u54cd\u5176\u4e0a\u6e38\u4fe1\u53f7\u6d3b\u6027\u3002\u4f8b\u5982\uff0ctrametinib\u53ef\u4ee5\u901a\u8fc7\u51cf\u5c11RAF-MEK\u86cb\u767d\u590d\u5408\u7269\u7684\u5f62\u6210\uff0c\u6765\u9650\u5236RAF\u4ecb\u5bfc\u7684MEK\u78f7\u9178\u5316\u3002\u7136\u800c\uff0ctrametinib\u6cbb\u7597\u4e5f\u80fd\u89c2\u5bdf\u5230MEK\u78f7\u9178\u5316\u7684\u53cd\u9988\u8c03\u8282\uff0c\u4e34\u5e8a\u4e0a\u4f1a\u51fa\u73b0trametinib\u6cbb\u7597\u540e\uff0c\u7531\u4e8e\u4e0a\u6e38\u4fe1\u53f7\u901a\u8def\u7a81\u53d8\u5f15\u8d77\u7684\u83b7\u5f97\u6027\u8010\u836f\uff08\u5982RAS\u7a81\u53d8\uff09\u3002MEK\u6291\u5236\u5242CH5126766\u53ef\u4ee5\u540c\u65f6\u6291\u5236MEK\u548cRAF\uff0c\u56e0\u4e3a\u5176\u4e0eMEK\u7684\u7ed3\u5408\u5bfc\u81f4\u5176\u6784\u8c61\u6539\u53d8\uff0c\u5e72\u6270\u4e86RAF\u4ecb\u5bfc\u7684MEK\u78f7\u9178\u5316\uff0c\u4ece\u800c\u4f7f\u5176\u4eceRAF-MEK\u590d\u5408\u7269\u4e2d\u91ca\u653e\uff0c\u65e9\u671f\u4e34\u5e8a\u6570\u636e\u8868\u660e\uff0c\u8fd9\u79cdMEK\u6291\u5236\u5242\u5bf9RAS\u7a81\u53d8\u80bf\u7624\u6d3b\u6027\u66f4\u9ad8\uff0c\u7279\u522b\u662f\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u3002\u53e6\u5916\uff0c\u50cfMAP855\u8fd9\u6837\u7684\u65b0\u578bMEK\u6291\u5236\u5242\u662fATP\u7ade\u4e89\u6027\u7684\uff0c\u5e76\u4e0e\u50ac\u5316\u4f4d\u70b9\u7ed3\u5408\u3002\u8fd9\u4e9b\u6291\u5236\u5242\u53ef\u80fd\u5bf9MEK\u6d3b\u5316\u72b6\u6001\u7684\u5dee\u5f02\u4e0d\u90a3\u4e48\u654f\u611f\u3002<\/span><\/p>\n<p><br  \/><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;font-size: 16px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"font-size: 17px;color: #ffffff;\"><strong>\u9776\u5411RAF\u548cMEK\u7a81\u53d8<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p><br  \/><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u5bf9BRAFV600\u764c\u75c7\u60a3\u8005\u7684\u9884\u5904\u7406\u548c\u6cbb\u7597\u4e2d\u80bf\u7624\u6d3b\u68c0\u7684\u836f\u6548\u5b66\u5206\u6790\u8868\u660e\uff0c\u8981\u4ea7\u751f\u4e34\u5e8a\u7597\u6548\u9700\u8981\u5bf9MAPK\u4fe1\u53f7\u8fdb\u884c\u6df1\u5ea6\u6291\u5236\u3002\u4e8b\u5b9e\u4e0a\uff0c\u65e9\u671fvemurafenib\u5bf9BRAFV600\u9ed1\u8272\u7d20\u7624\u7684\u4e34\u5e8a\u8bd5\u9a8c\u7684\u836f\u6548\u5b66\u7814\u7a76\u8868\u660e\uff0c\u6291\u5236&gt;80%\u7684ERK\u6d3b\u6027\u624d\u80fd\u8fbe\u5230\u6cbb\u7597\u6548\u679c\u3002\u56e0\u6b64\uff0c\u6cbb\u7597MAPK\u901a\u8def\u5f02\u5e38\u7684\u80bf\u7624\u7684\u9996\u8981\u76ee\u6807\u662f\u4ea7\u751f\u5f3a\u529b\u4e14\u6301\u7eed\u7684MAPK\u901a\u8def\u6291\u5236\u3002\u7279\u522b\u662f\uff0c\u5fc5\u987b\u4ed4\u7ec6\u8003\u8651MAPK\u901a\u8def\u6291\u5236\u5242\u5355\u72ec\u6216\u8054\u5408\u4f7f\u7528\u65f6\u7684\u6cbb\u7597\u6307\u6570\uff0c\u4ee5\u4fbf\u5728\u60a3\u8005\u53ef\u4ee5\u627f\u53d7\u7684\u836f\u7269\u6d53\u5ea6\u4e0b\uff0c\u5b9e\u73b0\u4fe1\u53f7\u901a\u8def\u7684\u5f3a\u70c8\u6291\u5236\u3002\u4e86\u89e3\u4fe1\u53f7\u751f\u7269\u5b66\u7684\u5173\u952e\u7279\u5f81\u4ee5\u53ca\u8bc6\u522b\u548c\u62e6\u622a\u80bf\u7624\u7ec6\u80de\u7ef4\u6301MAPK\u4fe1\u53f7\u8f93\u51fa\u7684\u673a\u5236\uff0c\u5bf9\u4e8e\u8bbe\u8ba1\u6709\u6548\u7684\u6cbb\u7597\u7b56\u7565\u81f3\u5173\u91cd\u8981\uff08\u56fe4\u3001\u56fe5\uff09\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><br  \/><\/span><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;font-size: 16px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"font-size: 17px;color: #ffffff;\"><strong>RAF\u7a81\u53d8<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><\/span><br  \/><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;font-size: 16px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"font-size: 17px;color: #ffffff;\"><strong>I\u7c7bBRAF\u7a81\u53d8\uff08BRAFV600\uff09<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><br  \/><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><br  \/><\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u76ee\u524d\uff0cRAF\u5355\u4f53\u6291\u5236\u5242\uff0c\u5305\u62ec\u4e09\u79cd\u7ecfFDA\u6279\u51c6\u7684\u836f\u7269vemurafenib\u3001dabrafenib\u548cencorafenib\uff0c\u8fd9\u4e00\u76f4\u662f\u6cbb\u7597BRAFV600\u7a81\u53d8\u578b\u764c\u75c7\u7684\u6838\u5fc3\u7b56\u7565\u3002\u8fd9\u4e9b\u836f\u7269\u5177\u6709\u76f8\u5bf9\u8f83\u5bbd\u7684\u6cbb\u7597\u7a97\u53e3\uff0c\u56e0\u4e3a\u5728BRAFV600\u80bf\u7624\u7ec6\u80de\u4e2d\uff0cBRAF\u4fe1\u53f7\u662f\u5355\u4f53\uff0c\u800c\u6b63\u5e38\u7ec6\u80de\u7684RAF\u4fe1\u53f7\u662f\u4e8c\u805a\u4f53\u3002\u6b63\u5e38\u7ec4\u7ec7\u4e2dERK\u4fe1\u53f7\u7684\u53cd\u5e38\u6fc0\u6d3b\u662f\u8fd9\u4e9b\u836f\u7269\u5bfc\u81f4\u589e\u751f\u6027\u76ae\u80a4\u75c5\u53d8\uff08\u5982\u89d2\u5316\u68d8\u76ae\u7624\uff09\u7684\u539f\u56e0\uff0cRAF\u6291\u5236\u5242\u4e0eMEK\u6291\u5236\u5242\u8054\u5408\u4f7f\u7528\u53ef\u4ee5\u6539\u5584\u6cbb\u7597\u6548\u679c\uff0c\u51cf\u8f7b\u76ae\u80a4\u6bd2\u6027\uff0c\u5e76\u964d\u4f4e\u8fd9\u4e9b\u589e\u751f\u6027\u76ae\u80a4\u75c5\u53d8\u7684\u53d1\u751f\u7387\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u7136\u800c\uff0c\u4e0d\u5b8c\u5168\u901a\u8def\u6291\u5236\u6216\u901a\u8def\u91cd\u65b0\u6fc0\u6d3b\u662fRAF\u6291\u5236\u5242\u7684\u4e3b\u8981\u95ee\u9898\u3002RAF\u6291\u5236\u5242\u6cbb\u7597\u540e\uff0c\u53cd\u9988\u6291\u5236\u5f15\u8d77\u7684RTK\u4fe1\u53f7\u7684\u91ca\u653e\uff0c\u5bfc\u81f4\u4e86RAF\u6291\u5236\u5242\u8010\u836f\u4e8c\u805a\u4f53\u7684\u5feb\u901f\u751f\u6210\uff0c\u5e76\u5bfc\u81f4\u4e86\u5bf9RAF\u6291\u5236\u5242\u7684\u9002\u5e94\u6027\u8010\u836f\u3002\u8054\u5408\u4f7f\u7528RAF\u548cMEK\u6291\u5236\u5242\u53ef\u63d0\u9ad8\u7597\u6548\uff0c\u56e0\u4e3aMEK\u6291\u5236\u53ef\u6291\u5236ERK\u518d\u6d3b\u5316\u3002\u5728\u5177\u6709\u9ad8\u57fa\u7840RTK\u4fe1\u53f7\u7684\u7ec4\u7ec7\u4e2d\uff0c\u9002\u5e94\u6027\u8010\u836f\u6700\u4e3a\u660e\u663e\u3002\u5728\u7ed3\u76f4\u80a0\u764c\u4e2d\uff0cEGFR\u4fe1\u53f7\u7684\u518d\u6fc0\u6d3b\u4f1a\u9650\u5236RAF\u6291\u5236\u5242\u7684\u6d3b\u6027\uff0cEGFR\u6291\u5236\u5242\u4e0eRAF\u6216RAF\/MEK\u6291\u5236\u5242\u7684\u8054\u7528\u53ef\u4ee5\u663e\u793a\u51fa\u66f4\u9ad8\u7684\u7597\u6548\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u5728\u63a5\u53d7\u9ad8\u98ce\u9669BRAFV600\u9ed1\u8272\u7d20\u7624\u5207\u9664\u672f\u7684\u60a3\u8005\u4e2d\uff0c\u8054\u5408\u4f7f\u7528RAF\u548cMEK\u6291\u5236\u5242\u53ef\u4ee5\u964d\u4f4e\u590d\u53d1\u98ce\u9669\uff0c\u56e0\u6b64\u8be5\u65b9\u6848\u53ef\u80fd\u53ef\u4ee5\u6839\u9664\u4e00\u4e9b\u60a3\u8005\u7684\u5fae\u8f6c\u79fb\u3002\u7136\u800c\uff0c\u5728\u8f6c\u79fb\u7684\u60c5\u51b5\u4e0b\uff0c\u51e0\u4e4e\u6240\u6709\u60a3\u8005\u6700\u7ec8\u90fd\u5bf9RAF\u6291\u5236\u5242\u6cbb\u7597\u4ea7\u751f\u8010\u836f\u6027\u3002\u8010\u836f\u6027\u901a\u5e38\u7531\u589e\u52a0RAF\u4e8c\u805a\u5316\u7684\u7a81\u53d8\u4ecb\u5bfc\uff0c\u4f8b\u5982RAS\u7a81\u53d8\u6216\u6269\u589e\u3001BRAFV600\u6269\u589e\u3001BRAF\u526a\u63a5\u53d8\u5f02\u3001\u589e\u52a0\u7684RTK\u4fe1\u53f7\u4ee5\u53ca\u589e\u52a0ERK\u6d3b\u5316\u7684MEK\u7a81\u53d8\u3002\u53e6\u5916\uff0cMEK\u6291\u5236\u5242\u6cbb\u7597\u540e\uff0c\u4f9d\u7136\u4f1a\u51fa\u73b0\u91cd\u65b0\u6fc0\u6d3bERK\u4fe1\u53f7\u7684\u7a81\u53d8\uff0c\u8fd9\u5c31\u5bfc\u81f4RAF\u6291\u5236\u5242\u4e0e\u76ee\u524d\u7684MEK\u6291\u5236\u5242\u8054\u5408\u4f7f\u7528\u4e5f\u4e0d\u662f\u6700\u4f73\u7684\u6cbb\u7597\u9009\u62e9\u3002\u6700\u65b0\u6570\u636e\u8868\u660e\uff0cERK\u6291\u5236\u5242\u53ef\u80fd\u66f4\u597d\u7684\u6291\u5236ERK\u4fe1\u53f7\uff0c\u5e76\u4e14\u5177\u6709\u66f4\u597d\u7684\u514b\u670d\u5e38\u89c1\u83b7\u5f97\u6027\u8010\u836f\u7684\u80fd\u529b\u3002\u65b0\u4e00\u4ee3RAF\u6291\u5236\u5242\uff08\u53ef\u80fd\u4e0eMEK\u6216ERK\u6291\u5236\u5242\u8054\u5408\u4f7f\u7528\uff09\uff0c\u662f\u5426\u5728\u6cbb\u7597BRAFV600\u80bf\u7624\u4e2d\u53d1\u6325\u5173\u952e\u4f5c\u7528\uff0c\u8fd9\u5c06\u9700\u8981\u8fdb\u4e00\u6b65\u7684\u4e34\u5e8a\u7814\u7a76\uff0c\u800c\u8fd9\u4e9b\u8054\u5408\u7528\u836f\u7684\u6cbb\u7597\u6307\u6570\u5c06\u662f\u7597\u6548\u7684\u5173\u952e\u3002\u5c3d\u7ba1MEK\u548cERK\u6291\u5236\u5242\u8054\u7528\u88ab\u8ba4\u4e3a\u6709\u6bd2\u6027\u4f5c\u7528\uff0c\u4f46RAF\u548cERK\u7ec4\u5408\u7684\u9996\u6b21\u7814\u7a76\u76ee\u524d\u6b63\u5728\u8fdb\u884c\u4e2d\uff08NCT02974725\uff09\u3002<\/span><\/p>\n<p style=\"text-align: center;\"><img class=\"rich_pages\"        style=\"width: 556px;height: auto;\" src=\"http:\/\/www.05921.net\/wp-content\/uploads\/2019\/04\/1-1554965994.jpeg\" alt=\"\u9776\u5411RAF-MEK\u901a\u8def\u4e2d\u7684\u7a81\u53d8\" title=\"\u9776\u5411RAF-MEK\u901a\u8def\u4e2d\u7684\u7a81\u53d8\"  \/><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: 15px;\">\u56fe4\uff1a\u9488\u5bf9\u4e0d\u540cBRAF\u7a81\u53d8\u7684\u6cbb\u7597\u7b56\u7565<\/span><\/p>\n<p style=\"text-align: center;\"><span style=\"font-size: 15px;\"><br  \/><\/span><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;font-size: 16px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"font-size: 17px;color: #ffffff;\"><strong>II\u7c7bBRAF\u7a81\u53d8<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p style=\"text-align: center;\"><span style=\"font-size: 15px;\"><\/span><br  \/><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u4e0e\u2160\u7c7bBRAF\u7a81\u53d8\u4e0d\u540c\uff0c\u2161\u7c7b\u7a81\u53d8\u5bf9RAF\u5355\u4f53\u6291\u5236\u5242\u5982vemurafenib\u4e0d\u654f\u611f\u3002\u7531\u4e8e\u8fd9\u4e9b\u836f\u7269\u5728\u4e34\u5e8a\u4e0a\u53ef\u8fbe\u5230\u7684\u5242\u91cf\u4e0b\u53ea\u7ed3\u5408\u4e8c\u805a\u4f53\u4e2d\u4e00\u4e2a\u539f\u805a\u4f53\uff0c\u56e0\u6b64\u5b83\u4eec\u5728\u542b\u6709\u8fd9\u4e9b\u7a81\u53d8\u4e8c\u805a\u4f53\u7684\u4fe1\u53f7\u901a\u8def\u4e2d\u4e0d\u80fd\u5145\u5206\u5730\u6291\u5236ERK\u4fe1\u53f7\u3002\u9488\u5bf9\u2161\u7c7b\u7a81\u53d8\u7684\u4e00\u79cd\u4e34\u5e8a\u7b56\u7565\u662f\u4f7f\u7528\u65b0\u578bRAF\u6291\u5236\u5242\uff0c\u4f8b\u5982RAF\u4e8c\u805a\u4f53\u6291\u5236\u5242\u6216RAF\u4e8c\u805a\u4f53\u65ad\u5f00\u5242\u3002\u8fd9\u4e9b\u6291\u5236\u5242\u80fd\u5e72\u6270\u6d3b\u5316BRAF\u4e8c\u805a\u4f53\u7684\u4fe1\u53f7\u4f20\u5bfc\uff0c\u5e76\u80fd\u6291\u5236\u8fd9\u4e9b\u6a21\u578b\u4e2d\u7684MAPK\u4fe1\u53f7\u4f20\u5bfc\u3002\u7531\u4e8e\u65b0\u4e00\u4ee3RAF\u6291\u5236\u5242\u6700\u8fd1\u624d\u8fdb\u5165\u4e34\u5e8a\uff0c\u76ee\u524d\u5c1a\u4e0d\u6e05\u695a\u8fd9\u4e9b\u836f\u7269\u662f\u5426\u53ef\u4ee5\u6cbb\u7597\u5177\u6709\u2161\u7c7bBRAF\u7a81\u53d8\u7684\u764c\u75c7\u3002\u53e6\u4e00\u79cd\u53ef\u80fd\u7684\u7b56\u7565\u662f\u963b\u65ad\u2161\u7c7bBRAF\u7a81\u53d8\u4e0b\u6e38\u7684MAPK\u4fe1\u53f7\u3002\u4e8b\u5b9e\u4e0a\uff0cMEK\u6291\u5236\u5242\u53ef\u4ee5\u5728II\u7c7bBRAF\u7a81\u53d8\u7684\u4e34\u5e8a\u524d\u6a21\u578b\u4e2d\u4fdd\u6301\u6291\u5236MAPK\u4fe1\u53f7\u7684\u80fd\u529b\uff0c\u4f46\u8fd9\u79cd\u65b9\u6cd5\u7684\u4e34\u5e8a\u7ecf\u9a8c\u662f\u6709\u9650\u7684\u3002\u540c\u6837\u7684\uff0cERK\u6291\u5236\u5242\u4e5f\u662f\u4e00\u79cd\u4e0b\u6e38MAPK\u963b\u65ad\u7684\u66ff\u4ee3\u65b9\u6cd5\u3002ERK1\/2\u6fc0\u9176\u6291\u5236\u5242ulixertinib\u7684\u4e00\u9879\u8bd5\u9a8c\uff0c\u7eb3\u516528\u4f8b\u975e-V600 BRAF\u7a81\u53d8\u60a3\u8005\u3002\u5728\u6d3b\u5316\u7684\u975e-V600 BRAF\u7a81\u53d8\u7684\u60a3\u8005\u4e2d\u53ef\u4ee5\u89c2\u5bdf\u5230\u4e34\u5e8a\u53cd\u5e94\uff0c\u8fd9\u4e9b\u60a3\u8005\u5305\u62ecBRAFL597Q\u80ba\u764c\u3001BRAFL458W\u80c6\u56ca\u764c\u3001BRAFG469A\u5934\u9888\u764c\u548cBRAFG469A\u5c0f\u80a0\u764c\u3002\u603b\u7684\u6765\u8bf4\uff0c33%\uff0815\u4f8b\u4e2d\u76845\u4f8b\uff09\u7684\u2161\u7c7bBRAF\u7a81\u53d8\u60a3\u8005\u5bf9ulixertinib\u6709\u90e8\u5206\u53cd\u5e94\u3002\u7136\u800c\uff0c\u572810\u4f8b\u2162\u7c7bBRAF\u7a81\u53d8\u60a3\u8005\u4e2d\u6ca1\u6709\u89c2\u5bdf\u5230\u53cd\u5e94\u3002\u5c3d\u7ba1\u9700\u8981\u8fdb\u4e00\u6b65\u7684\u4e34\u5e8a\u7814\u7a76\uff0c\u4f46\u8fd9\u4e9b\u65e9\u671f\u6570\u636e\u8868\u660e\uff0cMAPK\u901a\u8def\u7684\u4e0b\u6e38\u4fe1\u53f7\u6291\u5236\u53ef\u80fd\u662f\u67d0\u4e9b\u542b\u6709\u2161\u7c7bBRAF\u7a81\u53d8\u7684\u764c\u75c7\u7684\u6709\u6548\u4e34\u5e8a\u7b56\u7565\uff0c\u800c\u5177\u6709\u9ad8RAS\u6fc0\u6d3b\u7684\u2162\u7c7bBRAF\u7a81\u53d8\u7684\u7ec6\u80de\u4e2d\u7684\u53cd\u9988\u518d\u6fc0\u6d3b\u51cf\u5f31\u4e86\u8fd9\u79cd\u65b9\u6cd5\u7684\u6548\u679c\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><br  \/><\/span><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;font-size: 16px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"font-size: 17px;color: #ffffff;\"><strong>III\u7c7bBRAF\u7a81\u53d8<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><\/span><br  \/><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u540c\u6837\u5730\uff0c\u2162\u7c7bBRAF\u7a81\u53d8\u5bf9RAF\u5355\u4f53\u6291\u5236\u5242\uff08\u5982vemurafenib\uff09\u4e5f\u4e0d\u654f\u611f\u3002\u5bf9\u4e8e\u7a81\u53d8BRAF\/\u91ce\u751f\u578bRAF\u4e8c\u805a\u4f53\uff0cRAF\u6291\u5236\u5242\u4e0e\u4e8c\u805a\u4f53\u4e2d\u7a81\u53d8BRAF\u7684\u7ed3\u5408\u4f1a\u5bfc\u81f4\u91ce\u751f\u578bRAF\u7684\u8f6c\u5f55\u6fc0\u6d3b\u3002\u56e0\u6b64\uff0cRAF\u5355\u4f53\u6291\u5236\u5242\u5728\u8fd9\u4e9b\u7a81\u53d8\u5b58\u5728\u65f6\u4e0d\u80fd\u6291\u5236MAPK\u4fe1\u53f7\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">MAPK\u4fe1\u53f7\u7684\u4e0b\u6e38\u6291\u5236\u5242\uff08\u5373MEK\u548cERK\u6291\u5236\u5242\uff09\u5728\u5b58\u5728\u2162\u7c7b\u7a81\u53d8\u65f6\u53ef\u4ee5\u6291\u5236MAPK\u4fe1\u53f7\u3002\u7136\u800c\uff0cMAPK\u4e0b\u6e38\u4fe1\u53f7\u7684\u6291\u5236\u662f\u5426\u8db3\u4ee5\u8fbe\u5230\u6cbb\u7597\u80bf\u7624\u7684\u4e34\u5e8a\u6548\u5e94\uff0c\u4ee5\u53ca\u662f\u5426\u9700\u8981\u5728\u80bf\u7624\u4e2d\u540c\u65f6\u9776\u5411RTK\u4fe1\u53f7\u90fd\u5c1a\u4e0d\u6e05\u695a\u3002\u5982\u4e0a\u6240\u8ff0\uff0c\u80bf\u7624\u4e2d\u542b\u6709\u2162\u7c7bBRAF\u7a81\u53d8\u7684\u60a3\u8005\u5bf9ERK\u6291\u5236\u5242ulixertinib\u6ca1\u6709\u53cd\u5e94\uff0c\u53ef\u80fd\u662f\u56e0\u4e3a\u8fd9\u4e9b\u80bf\u7624\u4e2d\u9ad8RAS\u6fc0\u6d3b\u51cf\u5f31\u4e86ERK\u6291\u5236\u5242\u7684\u4f5c\u7528\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u56e0\u6b64\uff0c\u5bf9\u4e8e\u5177\u6709\u2162\u7c7bBRAF\u7a81\u53d8\u7684\u80bf\u7624\uff0c\u6709\u5e0c\u671b\u7684\u7b56\u7565\u662f\u4ee5\u2162\u7c7b\u7a81\u53d8\u4f5c\u4e3a\u201c\u4fe1\u53f7\u589e\u5f3a\u5242\u201d\u7684\u4e0a\u6e38\u4fe1\u53f7\u4e3a\u9776\u70b9\u3002\u8fd9\u5728\u5177\u6709\u91ce\u751f\u578bRAS\u548c\u663e\u6027RTK\u4fe1\u53f7\u7684\u80bf\u7624\u4e2d\u6700\u5bb9\u6613\u5b9e\u73b0\u3002\u4f8b\u5982\u7ed3\u76f4\u80a0\u764c\u7684\u2162\u7c7bBRAF\u7a81\u53d8\uff0c\u4e0e\u6297EGFR\u6297\u4f53\u5e94\u7528\u7684\u654f\u611f\u6027\u589e\u52a0\u548c\u751f\u5b58\u7387\u63d0\u9ad8\u6709\u5173\u3002\u56e0\u6b64\uff0c\u9776\u5411RTK\u53ef\u80fd\u662f\u4e00\u79cd\u6709\u6548\u4e14\u6613\u4e8e\u64cd\u4f5c\u7684\u9488\u5bf9\u2162\u7c7bBRAF\u7a81\u53d8\u80bf\u7624\u7684\u6cbb\u7597\u7b56\u7565\u3002\u7531\u4e8e\u80bf\u7624\u5e76\u4e0d\u4ec5\u4ec5\u5177\u6709\u5355\u4e00\u7684\u663e\u6027RTK\uff0c\u53ef\u80fd\u63a5\u6536\u591a\u91cdRTK\u7684\u4fe1\u53f7\uff0c\u963b\u65ad\u4e0a\u6e38\u4fe1\u53f7\u7684\u53e6\u4e00\u79cd\u65b9\u6cd5\u662f\u4f7f\u7528SHP2\u6291\u5236\u5242\uff0c\u540e\u8005\u963b\u65ad\u4e86\u591a\u91cdRTK\u7684\u5173\u952e\u5171\u540c\u6548\u5e94\u5668\u9776\u70b9\u3002SHP2\u6291\u5236\u5242\u8fd1\u671f\u5df2\u8fdb\u5165\u4e34\u5e8a\u7814\u7a76\u3002\u53e6\u5916\uff0c\u540c\u65f6\u9488\u5bf9\u4e0b\u6e38ERK\u6fc0\u6d3b\uff08\u4f7f\u7528MEK\u6216ERK\u6291\u5236\u5242\uff09\u548c\u4e0a\u6e38\u4fe1\u53f7\u4f20\u5bfc\uff08\u4f7f\u7528RTK\u6216SHP2\u6291\u5236\u5242\uff09\u7684\u8054\u5408\u6cbb\u7597\u65b9\u6cd5\u53ef\u80fd\u6210\u4e3a\u6f5c\u5728\u7684\u5177\u6709\u8fd9\u4e9b\u7a81\u53d8\u7684\u764c\u75c7\u7684\u6cbb\u7597\u7b56\u7565\u3002<\/span><\/p>\n<p><br  \/><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;font-size: 16px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"font-size: 17px;color: #ffffff;\"><strong>RAF\u878d\u5408\u4ee5\u53ca\u6846\u5185\u7f3a\u5931\u6fc0\u6d3b<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p><br  \/><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 14px;\">BRAF\u548cCRAF\uff08RAF1\uff09\u878d\u5408\u4e3b\u8981\u5bfc\u81f4C\u7aefRAF\u6fc0\u9176\u7ed3\u6784\u57df\u878d\u5408\u5230\u5177\u6709\u4e8c\u805a\u7ed3\u6784\u57df\u7684N\u7aef\u4f34\u4fa3\u4e0a\uff0c\u5bfc\u81f4\u72ec\u7acb\u4e8eRAS\u7684\u4e8c\u805a\u5316\uff0c\u5e76\u4e14\u6fc0\u6d3bRAF\u6fc0\u9176\u6d3b\u6027\u3002\u56e0\u6b64\uff0cRAF\u5355\u4f53\u6291\u5236\u5242\u5bf9BRAF\u6216CRAF\u878d\u5408\u65e0\u6548\u3002\u4e8b\u5b9e\u4e0a\uff0cRAF\u5355\u4f53\u6291\u5236\u5242\u53ef\u80fd\u901a\u8fc7\u4e8c\u805a\u4f53\u4f34\u4fa3\u7684\u53cd\u5f0f\u6fc0\u6d3b\u6765\u8bf1\u5bfcBRAF\u548cCRAF\u878d\u5408\u7ed3\u6784\u7684\u53cd\u5e38\u6fc0\u6d3b\u3002\u201c\u7279\u6b8a\u65ad\u5f00\u5242\u201dRAF\u6291\u5236\u5242\uff0c\u4f8b\u5982PLX8394\uff0c\u4e0d\u4f1a\u5bfc\u81f4BRAF\u878d\u5408\u7684\u7279\u6b8a\u6fc0\u6d3b\uff0c\u5e76\u4e14\u53ef\u4ee5\u901a\u8fc7\u7834\u574f\u542b\u6709BRAF\u7684\u4e8c\u805a\u4f53\u6765\u6291\u5236\u6fc0\u9176\u6d3b\u6027\u3002\u4f46\u662f\uff0cPLX8394\u4e0d\u80fd\u6291\u5236\u6765\u81eaCRAF\u878d\u5408\u4e8c\u805a\u4f53\u7684\u4fe1\u53f7\u4f20\u5bfc\uff0c\u5e76\u4e14\u5728\u8fd9\u79cd\u60c5\u51b5\u4e0b\u4f1a\u5bfc\u81f4CRAF\u4fe1\u53f7\u7684\u53cd\u5e38\u6fc0\u6d3b\u3002\u5728\u4e34\u5e8a\u524d\u6a21\u578b\u4e2d\uff0c\u4e00\u4e9bRAF\u4e8c\u805a\u4f53\u6291\u5236\u5242\u53ef\u4ee5\u7834\u574f\u6765\u81eaBRAF\u548cCRAF\u878d\u5408\u7684\u4fe1\u53f7\u3002\u56e0\u6b64\uff0cRAF\u4e8c\u805a\u4f53\u6291\u5236\u5242\u503c\u5f97\u5728\u8fd9\u79cd\u60c5\u51b5\u4e0b\u8fdb\u4e00\u6b65\u63a2\u7d22\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 14px;\">\u6b64\u5916\uff0c\u5728\u591a\u4e2a\u4e34\u5e8a\u6848\u4f8b\u4e2d\uff0c\u89c2\u5bdf\u5230\u4e0b\u6e38\u4fe1\u53f7MEK\u6291\u5236\u5242\u53ef\u80fd\u5177\u6709\u6cbb\u7597\u4f5c\u7528\u3002\u4e8b\u5b9e\u4e0a\uff0c\u7528MEK\u6291\u5236\u5242trametinib\u6cbb\u7597\u542b\u6709BRAF\u878d\u5408\u7684\u9ed1\u8272\u7d20\u7624\u60a3\u8005\u5df2\u7ecf\u89c2\u5bdf\u5230\u4e34\u5e8a\u53cd\u5e94\u3002\u7528ERK\u6291\u5236\u5242\u6291\u5236\u4e0b\u6e38MAPK\u4fe1\u53f7\u4e5f\u503c\u5f97\u8003\u8651\u7528\u4e8eBRAF\u878d\u5408\u764c\u75c7\u7684\u6cbb\u7597\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 14px;\">\u7c7b\u4f3c\u5730\uff0cBRAF \u03b23\u2013\u03b1C\u73af\u6846\u5185\u7f3a\u5931\u4e5f\u4f1a\u5bfc\u81f4BRAF\u6fc0\u9176\u6d3b\u5316\uff0c\u5e76\u4e14\u5bf9RAF\u5355\u4f53\u6291\u5236\u5242\u4e0d\u654f\u611f\u3002\u7279\u522b\u662f\uff0c\u4e00\u4e9bRAF\u6291\u5236\u5242\uff0c\u5982\u4f18\u5148\u7ed3\u5408\u975e\u6d3b\u6027\u201c\u03b1C-out\u201d\u6784\u8c61\u7684vemurafenib\uff0c\u5bf9\u8fd9\u4e9b\u7a81\u53d8\u4f53\u7ed3\u5408\u53d7\u635f\uff0c\u5728\u6d3b\u6027\u201c\u03b1C-in\u201d\u6784\u8c61\u4e2d\u53d7\u5230\u9650\u5236\u3002\u7136\u800c\uff0cRAF\u4e8c\u805a\u4f53\u6291\u5236\u5242\u4ee5\u53caRAF\u6291\u5236\u5242\u5982\u679c\u53ef\u4ee5\u4e0e\u201c\u03b1C-in\u201d\u6784\u8c61\u7ed3\u5408\uff0c\u5c31\u53ef\u4ee5\u5728\u8fd9\u4e9b\u6a21\u578b\u4e2d\u53d1\u6325\u6548\u5e94\u3002\u6b64\u5916\uff0c MEK\uff08\u6216ERK\uff09\u6291\u5236\u5242\u7684\u4e0b\u6e38\u4fe1\u53f7\u6291\u5236\u53ef\u4ee5\u6709\u6548\u5730\u6291\u5236\u7531\u8fd9\u4e9b\u7a81\u53d8\u4f53\u9a71\u52a8\u7684MAPK\u4fe1\u53f7\u3002\u6700\u8fd1\u7684\u4e00\u4efd\u62a5\u544a\u8be6\u7ec6\u63cf\u8ff0\u4e86\u4e00\u4f8bKRAS\u91ce\u751f\u578b\u80f0\u817a\u764c\u60a3\u8005\uff0c\u5176\u03b23\u2013\u03b1C\u73af\u4e2d\u5b58\u5728BRAF\u6846\u5185\u7f3a\u5931\uff0c\u8be5\u60a3\u8005\u63a5\u53d7trametinib\u6cbb\u7597\u5e76\u83b7\u5f97\u4e34\u5e8a\u7597\u6548\u3002\u6709\u8da3\u7684\u662f\uff0c\u5f53\u60a3\u8005\u5bf9trametinib\u4ea7\u751f\u83b7\u5f97\u6027\u8010\u836f\u65f6\uff0c\u5728\u65e0\u7ec6\u80deDNA\uff08cfDNA\uff09\u4e2d\u68c0\u6d4b\u5230\u4e09\u4e2aMEK2\u7a81\u53d8\uff0c\u8fd9\u8868\u660e\u8be5\u764c\u75c7\u9ad8\u5ea6\u4f9d\u8d56\u4e8eMAPK\u4fe1\u53f7\u4f20\u5bfc\uff0c\u5e76\u901a\u8fc7\u901a\u8def\u91cd\u6fc0\u6d3b\u800c\u53d8\u5f97\u8010\u836f\u3002\u503c\u5f97\u6ce8\u610f\u7684\u662f\uff0c\u968f\u540e\u7684ERK\u6291\u5236\u5242\u6cbb\u7597\u4f1a\u5bfc\u81f4\u8fd9\u4e9bcfDNA\u4e2dMEK2\u7a81\u53d8\u7684\u6c34\u5e73\u663e\u8457\u964d\u4f4e\u3002\u56e0\u6b64\uff0c\u5c3d\u7ba1\u9700\u8981\u8fdb\u4e00\u6b65\u7684\u4e34\u5e8a\u8bd5\u9a8c\uff0c\u4f46\u8fd9\u4e9b\u6570\u636e\u8868\u660eMEK\u6216ERK\u6291\u5236\u5242\u7684\u4e0b\u6e38\u4fe1\u53f7\u6291\u5236\u53ef\u80fd\u6210\u4e3a\u5177\u6709\u8fd9\u4e9b\u7a81\u53d8\u7684\u764c\u75c7\u7684\u6cbb\u7597\u7b56\u7565\u3002<\/span><\/p>\n<p><br  \/><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"color:#ffffff;\"><strong>MEK\u7a81\u53d8<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p><br  \/><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u4e0d\u540c\u7684MEK\u7a81\u53d8\u4f53\u5bf9\u76ee\u524d\u6279\u51c6\u7684MEK\u6291\u5236\u5242\u5177\u6709\u4e0d\u540c\u7684\u654f\u611f\u6027\uff0c\u5b83\u4eec\u90fd\u662fMEK\u53d8\u6784\u6291\u5236\u5242\u3002\u7136\u800c\uff0c\u6240\u6709\u7684MEK\u7a81\u53d8\u4f53\u4f3c\u4e4e\u90fd\u5bf9\u4e00\u7c7b\u65b0\u7684ATP\u7ade\u4e89\u6027MEK\u6fc0\u9176\u6291\u5236\u5242\u4fdd\u6301\u654f\u611f\uff0c\u8fd9\u79cd\u6291\u5236\u5242\u53ef\u4ee5\u7ed3\u5408\u50ac\u5316\u4f4d\u70b9\u6216ERK\u3002\u8fd9\u4e9b\u6570\u636e\u8868\u660e\uff0c\u5728\u4e34\u5e8a\u4e0a\u9776\u5411MEK\u7a81\u53d8\u7684\u80bf\u7624\u9700\u8981\u8003\u8651ERK\u6fc0\u6d3b\u7684\u673a\u5236\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><br  \/><\/span><\/p>\n<p style=\"text-align: center;\"><img class=\"rich_pages\"       style=\"width: 100%;height: auto;\"    src=\"http:\/\/www.05921.net\/wp-content\/uploads\/2019\/04\/10-1554965995.jpeg\" alt=\"\u9776\u5411RAF-MEK\u901a\u8def\u4e2d\u7684\u7a81\u53d8\" title=\"\u9776\u5411RAF-MEK\u901a\u8def\u4e2d\u7684\u7a81\u53d8\"  \/><span style=\"font-size: 15px;\">\u56fe5\uff1a\u9488\u5bf9\u4e0d\u540cMEK\u7a81\u53d8\u7684\u6cbb\u7597\u7b56\u7565<\/span><\/p>\n<p style=\"text-align: center;\"><br  \/><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"color:#ffffff;\"><strong>RAF-\u975e\u4f9d\u8d56\u578bMEK\u7a81\u53d8<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><\/span><br  \/><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">RAF-\u975e\u4f9d\u8d56\u578b\u7a81\u53d8\u4f53\u5bf9\u53d8\u6784MEK\u6291\u5236\u5242\uff0c\u5982trametinib\u3001cobimetinib\u3001binimetinib\u548cselumetinib\u4e0d\u654f\u611f\uff0c\u56e0\u4e3a\u8fd9\u4e9b\u836f\u7269\u4f18\u5148\u7ed3\u5408\u5230MEK1\u7684\u975e\u6d3b\u6027\u201c\u03b1C-out\u201d\u6784\u8c61\u3002\u8fd9\u4e9bMEK\u53d8\u4f53\u7684\u03b23\u2013\u03b1C\u73af\u77ed\u6846\u5185\u7f3a\u5931\u6291\u5236\u4e86\u6d3b\u6027\u201c\u03b1C-in\u201d\u6784\u8c61\u4e2d\u7684\u6fc0\u9176\uff0c\u964d\u4f4e\u4e86MEK\u53d8\u6784\u6291\u5236\u5242\u7684\u7ed3\u5408\u4eb2\u548c\u529b\u3002\u7136\u800c\uff0c\u8fd9\u4e9b\u7a81\u53d8\u4f53\u5bf9\u7ed3\u5408\u50ac\u5316\u4f4d\u70b9\u7684\u65b0\u578bATP\u7ade\u4e89\u6027MEK\u6291\u5236\u5242\u4fdd\u6301\u654f\u611f\u3002\u8fd9\u4e9b\u53d8\u4f53\u8fd8\u4fdd\u6301\u4e86\u5bf9\u4e0b\u6e38ERK\u6291\u5236\u5242\u7684\u654f\u611f\u6027\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><br  \/><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"color:#ffffff;\"><strong>RAF-\u8c03\u8282\u578bMEK\u7a81\u53d8<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><br  \/><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p style=\"text-indent: 2em;\"><br  \/><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u4e34\u5e8a\u524d\u7814\u7a76\u8868\u660e\uff0cRAF-\u8c03\u8282\u578bMEK\u7a81\u53d8\u53ef\u80fd\u4fdd\u7559\u5bf9MEK\u6291\u5236\u5242\u7684\u654f\u611f\u6027\uff0c\u56e0\u4e3a\u8fd9\u4e9b\u6291\u5236\u5242\u5728\u5177\u6709\u8fd9\u4e9b\u7a81\u53d8\u7684\u4e34\u5e8a\u524d\u6a21\u578b\u4e2d\uff0c\u53ef\u4ee5\u6291\u5236MAPK\u4fe1\u53f7\u3002\u6709\u4e34\u5e8a\u8bc1\u636e\u8868\u660e\uff0c\u67d0\u4e9bRAF-\u8c03\u8282\u578bMEK\u7a81\u53d8\uff08\u5373MEK1K57\u7a81\u53d8\uff09\u53ef\u80fd\u8868\u73b0\u51fa\u5bf9MEK\u6291\u5236\u5242\u7684\u4e34\u5e8a\u53cd\u5e94\u3002\u4e00\u4f4d\u60a3\u6709RAS\u91ce\u751f\u578b\u7ed3\u76f4\u80a0\u764c\u7684\u60a3\u8005\uff0c\u5bf9\u6297EGFR\u6297\u4f53\u897f\u59a5\u6614\u5355\u6297\u7684\u957f\u671f\u7f13\u89e3\u4e4b\u540e\uff0c\u51fa\u73b0\u4e86\u4e00\u79cdMEK1K57T\u7a81\u53d8\uff0c\u4ece\u800c\u4ea7\u751f\u83b7\u5f97\u6027\u8010\u836f\u3002\u5728\u6297EGFR\u6cbb\u7597\u4e2d\u6dfb\u52a0MEK\u6291\u5236\u5242trametinib\uff0c\u53ef\u4ee5\u4f7fMEK1K57T\u7a81\u53d8\u80bf\u7624\u75c5\u53d8\u6d88\u9000\uff0c\u5e76\u4e14\u5728\u5e8f\u5217cfDNA\u4e2dMEK1K57T\u7684\u53ef\u68c0\u6d4b\u53d8\u5f02\u7b49\u4f4d\u57fa\u56e0\u9891\u7387\u663e\u8457\u964d\u4f4e\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">\u7136\u800c\uff0c\u4e5f\u6709\u4e34\u5e8a\u8bc1\u636e\u8868\u660e\uff0cMEK\u6291\u5236\u5242\u53ef\u80fd\u65e0\u6cd5\u514b\u670dRAF-\u8c03\u8282\u578bMEK\u7a81\u53d8\u3002\u7528RAF\u548cMEK\u6291\u5236\u5242\u8054\u7528\u6cbb\u7597BRAFV600\u7a81\u53d8\u7684\u9ed1\u8272\u7d20\u7624\u548c\u7ed3\u76f4\u80a0\u764c\u540e\u51fa\u73b0\u7684\u83b7\u5f97\u6027\u8010\u836f\u4e2d\uff0c\u5df2\u7ecf\u53d1\u73b0\u4e86\u90e8\u5206\u8fd9\u7c7b\u7a81\u53d8\u3002\u7531\u4e8e\u8fd9\u4e9b\u7a81\u53d8\u4f53\u7684\u6d3b\u6027\u53ef\u4ee5\u901a\u8fc7\u589e\u52a0\u7684RAF\u4ecb\u5bfc\u7684\u78f7\u9178\u5316\u6765\u589e\u5f3a\uff0c\u81ea\u9002\u5e94\u53cd\u9988\u8c03\u8282\u53ef\u80fd\u4f1a\u4f7fMEK\u6291\u5236\u5242\u5728\u6301\u7eed\u7684\u4e0a\u6e38\u4fe1\u53f7\u7684\u4f5c\u7528\u4e0b\u6548\u679c\u53d8\u5dee\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">ERK\u6291\u5236\u5242\u53ef\u80fd\u6210\u4e3a\u514b\u670d\u8fd9\u4e9b\u7a81\u53d8\u7684\u4e00\u79cd\u6f5c\u5728\u7684\u6cbb\u7597\u7b56\u7565\u3002\u4e34\u5e8a\u524d\u7814\u7a76\u8868\u660e\uff0cERK\u6291\u5236\u5242\u5728\u8fd9\u4e9bMEK\u7a81\u53d8\u7684\u5b58\u5728\u4e0b\u4ecd\u7136\u6709\u6548\u3002\u6700\u8fd1\u7684\u4e00\u9879\u7814\u7a76\u8868\u660e\uff0cRAF\u548cMEK\u6291\u5236\u5242\u8054\u5408\u4f7f\u7528\u4e0d\u80fd\u6291\u5236\u542b\u6709MEK1K57\u548cMEK1F53\u7a81\u53d8\u7684BRAFV600\u7ed3\u76f4\u80a0\u764c\u7ec6\u80de\u7684\u4f53\u5916\u751f\u957f\uff0c\u4f46ERK\u6291\u5236\u5242\u5355\u72ec\u4f7f\u7528\u6216RAF\u548cERK\u6291\u5236\u5242\u8054\u5408\u4f7f\u7528\u53ef\u4ee5\u5b8c\u5168\u6291\u5236\u5176\u4f53\u5916\u751f\u957f\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><br  \/><\/span><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"color:#ffffff;\"><strong>RAF-\u4f9d\u8d56\u578bMEK\u7a81\u53d8<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p style=\"text-indent: 2em;\"><br  \/><span style=\"font-size: 15px;\"><\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">MEK\u548cERK\u6291\u5236\u5242\u5177\u6709\u6291\u5236\u7531\u8fd9\u7c7bMEK\u7a81\u53d8\u9a71\u52a8\u7684MAPK\u4fe1\u53f7\u7684\u80fd\u529b\uff0c\u56e0\u6b64\u53ef\u80fd\u4f1a\u6210\u4e3a\u4e00\u79cd\u6f5c\u5728\u7684\u6cbb\u7597\u7b56\u7565\u3002\u7136\u800c\uff0c\u8fd9\u4e9bMEK\u7a81\u53d8\u4f53\u901a\u5e38\u8ba4\u4e3a\u662f\u201c\u4fe1\u53f7\u589e\u5f3a\u5242\u201d\uff0c\u5e76\u5728\u591a\u6570\u60c5\u51b5\u4e0b\u4e0e\u4e0a\u6e38\u6fc0\u6d3b\u7a81\u53d8\u5171\u5b58\uff0c\u5e38\u89c1\u7684\u662fBRAFV600\u7a81\u53d8\u3002\u56e0\u6b64\uff0c\u9776\u5411\u4e0a\u6e38\u4f18\u52bf\u4fe1\u53f7\uff0c\u5e76\u7ed3\u5408MEK\u6216ERK\u7684\u4e0b\u6e38\u963b\u65ad\u53ef\u80fd\u662f\u4e00\u79cd\u6700\u4f73\u65b9\u6cd5\u3002\u4f8b\u5982\uff0c\u5728\u540c\u65f6\u5b58\u5728\u8fd9\u7c7b\u7a81\u53d8\u7684BRAFV600\u764c\u75c7\u4e2d\uff0cRAF\u6291\u5236\u5242\u4e0eMEK\u6216ERK\u6291\u5236\u5242\u7684\u8054\u7528\u53ef\u80fd\u662f\u6700\u4f73\u9009\u62e9\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><br  \/><\/p>\n<section class=\"_editor\">\n<section style=\"margin-top: 10px;margin-bottom: 10px;\">\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-right: -5px;margin-left: -5px;padding: 5px 10px;letter-spacing: 1.5px;box-sizing: border-box;background-color: #b0aadf;box-shadow: #a3a3a3 2px 2px 5px;transform: rotateZ(0deg);\">\n<p style=\"letter-spacing: 2px;\"><span style=\"color:#ffffff;\"><strong>\u603b\u7ed3<\/strong><\/span><\/p>\n<\/section>\n<section>\n<section style=\"display: flex;justify-content:center;align-items: center;\">\n<section style=\"width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<section style=\"margin-left:2px;width:10px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<section style=\"margin-top:5px;width:30px;height:5px;background-color:#b0aadf;\"><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\"><\/span><br  \/><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"font-size: 15px;\">MAPK\u901a\u8def\u5728\u4eba\u7c7b\u764c\u75c7\u4e2d\u8d77\u7740\u5173\u952e\u4f5c\u7528\uff0c\u53ef\u4ee5\u901a\u8fc7\u591a\u79cd\u4e0d\u540c\u7684\u673a\u5236\u5728\u591a\u6570\u764c\u75c7\u4e2d\u88ab\u4e0d\u5f53\u6fc0\u6d3b\u3002\u7136\u800c\uff0c\u7531\u4e8eMAPK\u901a\u8def\u7684\u590d\u6742\u751f\u7269\u5b66\u4fe1\u53f7\uff0c\u4ee5\u53ca\u4e0b\u6e38\u901a\u8def\u6210\u5206\u5982RAF\u548cMEK\u7684\u4e0d\u540c\u7a81\u53d8\uff0c\u4f1a\u4ea7\u751f\u622a\u7136\u4e0d\u540c\u7684\u4fe1\u53f7\u7279\u6027\u3002\u8fd1\u5e74\u6765\uff0c\u5173\u4e8eMAPK\u4fe1\u53f7\u901a\u8def\u7684\u751f\u7269\u5316\u5b66\u548c\u529f\u80fd\u5b66\u7684\u6df1\u5165\u63a2\u7d22\uff0c\u4e3a\u521b\u9020\u65b0\u7684\u6cbb\u7597\u624b\u6bb5\u5960\u5b9a\u57fa\u7840\u3002\u540c\u65f6\uff0c\u672a\u6765\u9488\u5bf9RAF\u6216MEK\u7a81\u53d8\u7684\u65b0\u6cbb\u7597\u7b56\u7565\u7684\u4e34\u5e8a\u8bd5\u9a8c\u5e94\u5305\u62ec\u8be6\u7ec6\u7684\u836f\u6548\u5b66\u8bc4\u4f30\uff0c\u901a\u8fc7\u914d\u5bf9\u7684\u9884\u5904\u7406\u548c\u6cbb\u7597\u4e2d\u7684\u80bf\u7624\u6d3b\u68c0\uff0c\u4ee5\u786e\u5b9a\u9488\u5bf9\u4e0d\u540c\u9776\u70b9\u7684\u6cbb\u7597\u65b9\u6cd5\u7684\u7279\u5b9a\u7597\u6548\u3002\u603b\u7684\u6765\u8bf4\uff0c\u5bf9\u7279\u5b9a\u7684RAF\u548cMEK\u7a81\u53d8\u7684\u4fe1\u53f7\u7279\u5f81\u7684\u6df1\u5165\u7406\u89e3\u5bf9\u4e8e\u5f00\u53d1\u6709\u6548\u7597\u6cd5\u81f3\u5173\u91cd\u8981\u3002<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"color: rgb(136, 136, 136);font-size: 12px;\"><br  \/><\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"color: rgb(136, 136, 136);font-size: 12px;\">\u53c2\u8003\u6587\u732e<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"color: rgb(136, 136, 136);font-size: 12px;\">1\u3001Rona Yaeger and Ryan B. Corcoran. Targeting Alterations in the RAF-MEK Pathway. Cancer Discovery, Published OnlineFirst February 15, 2019<\/span><\/p>\n<p style=\"text-indent: 2em;\"><span style=\"color: rgb(136, 136, 136);font-size: 12px;\">2\u3001\u9648\u5efa\u52c7, \u738b\u806a, \u738b\u5a1f\u7b49. MAPK\u4fe1\u53f7\u901a\u8def\u7814\u7a76\u8fdb\u5c55. \u4e2d\u56fd\u533b\u836f\u79d1\u5b66, 2011, 1(8), 32-34<\/span><\/p>\n<\/p><\/div>\n","protected":false},"excerpt":{"rendered":"<p>MAPK\u901a\u8def\u662f\u764c\u75c7\u4e2d\u6700\u5e38\u89c1\u7684\u7a81\u53d8\u81f4\u764c\u9014\u5f84\u4e4b\u4e00\u3002\u5c3d\u7ba1RAS\u7a81\u53d8\u5728MAPK\u901a\u8def\u6539\u53d8\u4e2d\u6700\u5e38\u89c1\uff0c\u4f46\u662f\u76f8\u5bf9\u6765\u8bf4\u7a81\u53d8\u8f83\u4e0d\u9891 [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":82330,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/82329"}],"collection":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/comments?post=82329"}],"version-history":[{"count":1,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/82329\/revisions"}],"predecessor-version":[{"id":82336,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/82329\/revisions\/82336"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media\/82330"}],"wp:attachment":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media?parent=82329"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/categories?post=82329"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/tags?post=82329"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}