經(jīng)過多年的努力，科學(xué)家們?cè)卺槍?duì)幾種惡性腫瘤的KRAS突變方面已經(jīng)取得了多向進(jìn)展:

After decades of efforts, scientists have made progress into targeting KRAS mutations in several malignancies.

在1967年, Ha-Ras 和 Ki-Ras逆轉(zhuǎn)錄病毒轉(zhuǎn)化基因被發(fā)現(xiàn)，它們對(duì)應(yīng)的人類RAS家族HRAS和KRAS于1982年被發(fā)現(xiàn).

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 與肺癌的關(guān)系于1984年被首次描述，這些年KRAS 突變?cè)诜伟┲幸呀?jīng)有多項(xiàng)進(jìn)展。突變的KRAS被持續(xù)性激活，并導(dǎo)致持續(xù)的下游信號(hào)傳導(dǎo)和腫瘤發(fā)生。

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.

在2013年隨著對(duì)KRAS生物學(xué)的了解加深和藥物設(shè)計(jì)技術(shù)的更新，科學(xué)家們?cè)贕DP結(jié)合的突變型KRAS G12C 蛋白中發(fā)現(xiàn)了半胱氨酸藥物結(jié)合袋。

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.

在2021年，科學(xué)家們成功開發(fā)出阻斷突變型KRAS G12C 的共價(jià)抑制劑。2021年5月，Sotorasib獲得FDA批準(zhǔn)，用于治療KRAS G12C突變的NSCLC，這是第一個(gè)獲批的KRAS G12C抑制劑，目前還有更多藥物正在研發(fā)中。

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。

KRAS新藥研發(fā)平臺(tái)

什么是KRAS?

KRAS的信號(hào)通路

美迪西助力信諾維抗腫瘤1類新藥XNW14010（小分子KRAS G12C蛋白共價(jià)結(jié)合抑制劑）獲批臨床