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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.
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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.
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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.
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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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