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After decades of efforts, scientists have made progress into targeting KRAS mutations in several malignancies.
ÔÚ1967Äê, Ha-Ras ºÍ Ki-RasÄæ×ªÂ¼²¡¶¾×ª»¯»ùÒò±»·¢Ã÷£¬£¬£¬£¬£¬ËüÃǶÔÓ¦µÄÈËÀàRAS¼Ò×åHRASºÍKRASÓÚ1982Äê±»·¢Ã÷.
In 1967, Ha-Ras and Ki-Ras retroviral transforming genes were discovered.Their human counterparts,Ha-Ras and Ki-Ras ,were discovered in 1982.
KRAS Óë·Î°©µÄ¹ØÏµÓÚ1984Äê±»Ê×´ÎÐÎò£¬£¬£¬£¬£¬ÕâЩÄêKRAS Í»±äÔڷΰ©ÖÐÒѾÓжàÏîÏ£Íû¡£¡£¡£Í»±äµÄKRAS±»Ò»Á¬ÐÔ¼¤»î£¬£¬£¬£¬£¬²¢µ¼ÖÂÒ»Á¬µÄÏÂÓÎÐźŴ«µ¼ºÍÖ×Áö±¬·¢¡£¡£¡£
The relationship between KRAS and lung cancer was described in 1984,KRAS mutation in lung cancer has progressed.Mutant KRAS is constitutively activated and leads to persistent downstream signalling and oncogenesis.
ÔÚ2013ÄêËæ×ŶÔKRASÉúÎïѧµÄÏàʶ¼ÓÉîºÍÒ©ÎïÉè¼Æ¼¼ÊõµÄ¸üУ¬£¬£¬£¬£¬¿ÆÑ§¼ÒÃÇÔÚGDPÁ¬ÏµµÄÍ»±äÐÍKRAS G12C ÂѰ×Öз¢Ã÷Á˰ëë×°±ËáÒ©ÎïÁ¬Ïµ´ü¡£¡£¡£
In 2013 improved understanding of KRAS biology and newer drug designing technologies led to crucial discovery of a cysteins drug binding pocket in GDP-bound mutant KRAS G12C protein.
ÔÚ2021Ä꣬£¬£¬£¬£¬¿ÆÑ§¼ÒÃÇÀֳɿª·¢³ö×è¶ÏÍ»±äÐÍKRAS G12C µÄ¹²¼ÛÒÖÖÆ¼Á¡£¡£¡£2021Äê5Ô£¬£¬£¬£¬£¬Sotorasib»ñµÃFDAÅú×¼£¬£¬£¬£¬£¬ÓÃÓÚÖÎÁÆKRAS G12CÍ»±äµÄNSCLC£¬£¬£¬£¬£¬ÕâÊǵÚÒ»¸ö»ñÅúµÄKRAS G12CÒÖÖÆ¼Á£¬£¬£¬£¬£¬ÏÖÔÚÉÐÓиü¶àÒ©ÎïÕýÔÚÑз¢ÖС£¡£¡£
In 2021,covalent inhibitors that block mutant KRAS G12C were successfully developed.In May 2021 the US FDA granted accelerated approval to Sotorasib(1st KRAS G12C inhibitor)£¬£¬£¬£¬£¬for the treatment of adults with advanced NSCLC with KRAS G12C mutation.Sotorasib was the first KRAS G12C inhibitor to be approved£¬£¬£¬£¬£¬with several more in the pipeline¡£¡£¡£
ÃÀ¸ß÷ÖúÁ¦ÐÅŵά¿¹Ö×Áö1ÀàÐÂÒ©XNW14010£¨Ð¡·Ö×ÓKRAS G12CÂѰ׹²¼ÛÁ¬ÏµÒÖÖÆ¼Á£©»ñÅúÁÙ´²
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