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KRASÒÖÖÆ¼ÁµÄÉú³¤Àú³Ì

2024-01-08
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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©ÎïÉè¼ÆÊÖÒյĸüУ¬¿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¢ÖÐ ¡£

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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