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01 RETÏà¹ØÐźÅͨ·

RET(rearranged during transfection)ÊÇÒ»¸öÔ­°©»ùÒò £¬£¬Î»ÓÚ10ºÅȾɫÌ峤±Û £¬£¬±àÂëÒ»ÖÖÊÜÌåÀÒ°±Ëἤø(RTK)¡£¡£¡£¡£Í¨³£ £¬£¬½ºÖÊϸ°ûÔ´ÐÔÉñı»®ÑøÒò×Ó(Glial cell-line derived neurotrophic factor, GDNF)Ê×ÏÈÓëGFR¦Á1Á¬ÏµÐγÉGDNF-GFR¦Á1¸´ºÏÎï £¬£¬¸Ã¸´ºÏÎïÔÙÓëRETÁ¬ÏµÐγÉÈý¾ÛÌ帴ºÏÎï £¬£¬µ¼ÖÂRETµÄ¶þ¾Û»¯ £¬£¬½øÒ»²½ÒýÆðÀÒ°±Ëá²Ð»ù×ÔÁ×Ëữ £¬£¬´Ó¶ø¼¤»îÏÂÓÎÐźÅͨ·¡£¡£¡£¡£RETÏÂÓÎÏà¹ØÐźÅͨ·Ö÷Òª°üÀ¨RAS-MAPKºÍPI3K¨CAKTµÈ¡£¡£¡£¡£

 

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02 RET°ÐµãÓëÏà¹Ø°©Ö¢

RET»ùÒòÒì³£»£»£»£» £» £»î»¯Ö÷Òª°üÀ¨»ùÒòÈںϡ¢µãÍ»±ä¡¢¹ý±í´ïÈýÖÖ»úÖÆ £¬£¬¿Éµ¼Ö¶àÖÖ°©Ö¢¡£¡£¡£¡£RET»ùÒòµãÍ»±äÔÚ¼××´ÏÙËèÑù°©(MTC)Öеı¬·¢ÂÊԼΪ60%-90% £¬£¬ÆäÖÐ×î³£¼ûµÄÍ»±äλµãÊÇM918T¡£¡£¡£¡£RET»ùÒòÈÚºÏÔÚ¼××´ÏÙÈéÍ·×´°©(PTC)Öб¬·¢ÂÊΪ10%-20%;ÔÚ·ÇСϸ°û·ÎÏÙ°©»¼ÕßÖеı¬·¢ÂÊԼΪ1-2% £¬£¬ÆäÖÐÒÔKIF5B-RET×îΪ¶à¼û¡£¡£¡£¡£

 

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03 RET ÒÖÖƼÁÑз¢Ã÷×´

ÏÖÔÚ¹ØÓÚRET»ùÒò¸Ä±äÀàÖ×ÁöµÄÖÎÁÆ·½°¸Ö÷ÒªÊÇʹÓöà°Ðµã¼¤Ã¸ÒÖÖƼÁÀàÒ©Îï £¬£¬ºÃ±È¿¨²©ÌæÄá¡¢·²µÂËûÄá £¬£¬ÕâЩҩÎï²»µ«ÒÖÖÆRETÂÑ°× £¬£¬Í¬Ê±»áÒÖÖÆVEGFR¡¢EGFRµÈÆäËûÂѰס£¡£¡£¡£2020Äê5ÔÂ8ÈÕ £¬£¬FDA¼ÓËÙÅú×¼ÁËÈ«ÇòÊ׸ö¸ßÑ¡ÔñÐÔRET¼¤Ã¸ÒÖÖƼÁLOXO-292 (selpercatinib £¬£¬ÀñÀ´) £¬£¬ºÍÆäËû°ÐÏòÒ©Ò»Ñù £¬£¬LOXO-292Ò²»áÄÍÒ©¡£¡£¡£¡£ÁÙ´²Ç°Ñо¿ÏÔʾ £¬£¬RETÈÚºÏNSCLC»¼ÕßʹÓÃLOXO-292ÖÎÁÆºó £¬£¬¿É±¬·¢G810R/S/CÈܼÁÇ°ÑØÍ»±ä £¬£¬µ¼ÖÂLOXO-292ÄÍÒ©¡£¡£¡£¡£

ÓÉTurning Point Therapeutics¹«Ë¾¿ª·¢µÄС·Ö×ÓÖƼÁTPX-0046µÄÁÙ´²Ç°Ñо¿Ð§¹ûÏÔʾÆä¶ÔRET-G810R/SÍ»±ä½ÏΪÃô¸Ð £¬£¬ÒÑ¿ªÕ¹Ò»ÆÚÁÙ´²ÊµÑé £¬£¬ÁíÒ»¿î¿ª·¢ËÙÂʽϿìµÄRETÒÖÖƼÁBLU-667 (pralsetinib £¬£¬Blueprint¹«Ë¾)ÒÑÏòFDAÌá½»ÁËÉÏÊÐÉêÇë¡£¡£¡£¡£

 

04 ²¿·Öϸ°ûÑéÖ¤Êý¾Ý

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2)Ba/F3-KIF5B-RET-V804MÑéÖ¤Êý¾Ý

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3)Ba/F3-KIF5B-RET-V804LÑéÖ¤Êý¾Ý

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4)Ba/F3-KIF5B-RET-G810RÑéÖ¤Êý¾Ý

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5)Ba/F3-KIF5B-RET-G810SÑéÖ¤Êý¾Ý

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6)Ba/F3-KIF5B-RET-G810CÑéÖ¤Êý¾Ý

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ͼƬȪԴ¼Î¿½å¼ÎÄÏ×£º

¡¾1¡¿Advances in Targeting RET-Dependent Cancers. Cancer Discov. ,2020,10:498¨C505.

¡¾2¡¿RET Solvent Front Mutations Mediate Acquired Resistance to Selective RET Inhibition in RET-Driven Malignancies. J.Thorac. Oncol.;2020, 15:541-549.

 

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