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KRASÒÖÖÆ¼ÁµÄÉú³¤Àú³Ì

2024-01-08
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¾­ÓɶàÄêµÄÆð¾¢£¬ £¬£¬£¬£¬¿ÆÑ§¼ÒÃÇÔÚÕë¶Ô¼¸ÖÖ¶ñÐÔÖ×ÁöµÄKRASÍ»±ä·½ÃæÒѾ­È¡µÃÁ˶àÏòÏ£Íû:

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¡£¡£¡£

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