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Íú²Æ28 Ba/F3-RET ϸ°ûÖê

 

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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¸´ºÏÎ£¬£¬£¬¸Ã¸´ºÏÎïÔÙÓëRETÁ¬ÏµÐγÉÈý¾ÛÌ帴ºÏÎ£¬£¬£¬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 ÒÖÖÆ¼ÁÑз¢Ã÷×´

ÏÖÔÚ¹ØÓÚRET»ùÒò¸Ä±äÀàÖ×ÁöµÄÖÎÁƼƻ®Ö÷ÒªÊÇʹÓöà°Ðµã¼¤Ã¸ÒÖÖÆ¼ÁÀàÒ©Î£¬£¬£¬ºÃ±È¿¨²©ÌæÄá¡¢·²µÂËûÄᣬ£¬£¬£¬ÕâЩҩÎï²»µ«ÒÖÖÆRETÂѰ×£¬£¬£¬£¬Í¬Ê±»áÒÖÖÆVEGFR¡¢EGFRµÈÆäËûÂѰס£¡£2020Äê5ÔÂ8ÈÕ£¬£¬£¬£¬FDA¼ÓËÙÅú×¼ÁËÈ«ÇòÊ׸ö¸ßÑ¡ÔñÐÔRET¼¤Ã¸ÒÖÖÆ¼ÁLOXO-292 (selpercatinib £¬£¬£¬£¬ÀñÀ´)£¬£¬£¬£¬ºÍÆäËû°ÐÏòÒ©Ò»Ñù£¬£¬£¬£¬LOXO-292Ò²»áÄÍÒ©¡£¡£ÁÙ´²Ç°Ñо¿ÏÔʾ£¬£¬£¬£¬RETÈÚºÏNSCLC»¼ÕßʹÓÃLOXO-292ÖÎÁƺ󣬣¬£¬£¬¿É±¬·¢G810R/S/CÈܼÁÇ°ÑØÍ»±ä£¬£¬£¬£¬µ¼ÖÂLOXO-292ÄÍÒ©¡£¡£

ÓÉTurning Point Therapeutics¹«Ë¾¿ª·¢µÄС·Ö×ÓÖÆ¼ÁTPX-0046µÄÁÙ´²Ç°Ñо¿Ð§¹ûÏÔʾÆä¶ÔRET-G810R/SÍ»±ä½ÏΪÃô¸Ð£¬£¬£¬£¬ÒÑ¿ªÕ¹Ò»ÆÚÁÙ´²ÊµÑ飬£¬£¬£¬ÁíÒ»¿î¿ª·¢ËÙÂʽϿìµÄRETÒÖÖÆ¼ÁBLU-667 (pralsetinib £¬£¬£¬£¬Blueprint¹«Ë¾)ÒÑÏòFDAÌá½»ÁËÉÏÊÐÉêÇë¡£¡£

 

04 ²¿·Öϸ°ûÑéÖ¤Êý¾Ý

1)Ba/F3-KIF5B-RETÑéÖ¤Êý¾Ý

 

2)Ba/F3-KIF5B-RET-V804MÑéÖ¤Êý¾Ý

 

3)Ba/F3-KIF5B-RET-V804LÑéÖ¤Êý¾Ý

 

4)Ba/F3-KIF5B-RET-G810RÑéÖ¤Êý¾Ý

 

5)Ba/F3-KIF5B-RET-G810SÑéÖ¤Êý¾Ý

 

6)Ba/F3-KIF5B-RET-G810CÑéÖ¤Êý¾Ý

 

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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