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ZHAO Leilei, ZHANG Yuan, ZHOU Jinpei, ZHANG Huibin. Advances in research on drugs targeting non-small cell lung cancer[J]. Journal of China Pharmaceutical University, 2014, 45(2): 136-144. DOI: 10.11665/j.issn.1000-5048.20140202
Citation: ZHAO Leilei, ZHANG Yuan, ZHOU Jinpei, ZHANG Huibin. Advances in research on drugs targeting non-small cell lung cancer[J]. Journal of China Pharmaceutical University, 2014, 45(2): 136-144. DOI: 10.11665/j.issn.1000-5048.20140202

Advances in research on drugs targeting non-small cell lung cancer

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  • With the continuous development of molecular biology, people have gained a deeper understanding of non-small cell lung cancer(NSCLC). Researchers have found that multiple oncogenic driver mutations are closely associated with the development, progression and prognosis of NSCLC, such as EGFR mutations, ALK rearrangement, KRAS mutations, c-MET amplification, FGFR1 amplification, PIK3CA mutations, BRAF mutations, ERBB2 amplification, and DDR2 mutation. Adenocarcinoma(ADC)and squamous cell carcinoma(SCC)are two most common subtypes of NSCLC. In this review, we choose targeted therapy drugs of ADC and SCC as an entry point to introduce several potential targets and small molecule inhibitors for the treatment of NSCLC, including EGFR inhibitors, ALK inhibitors, KRAS inhibitors, c-MET inhibitors, FGFR1 inhibitors, PI3K inhibitors, BRAF inhibitors, ERBB2 inhibitors and DDR2 inhibitors. We hope this review will be a helpful guide to clinicians and researchers alike by assisting in therapy decision making and acting as a platform for further study.
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    Zhou W,Ercan D,Chen L,e汴礠?楬渼?灩栾愮獎敯???愠湭摵?灡桮慴猭敳???捣汴楩湶楥挠慅汇?瑒爠楫慩汮獡孳?崠??楨????敯摲??桡敧浡??楳???ぇ????户?????扝????????????? ̄?????戬爼??嬴财?崼???栨爷攠渲搷琶?区???攷挰欭攱爠‰倷???汢慲眯椾?????椠?敵琠?愬汚??楮???椬杘慵爠敓琬琼敩 ̄獥浴漠歡楬渼术?椾献?獹瑲物潭湩杤汯祛?愬猵猭潤捝椠慰瑹敲摩?睩楤瑩桮?洴用琱愼瑩椾潈渼?潩显?琭桯敮???牥慲獩?条整湩敶?楳渠?灳愠瑳楥敬湥瑣獴?睶楥琠桩?灨物楢浩慴牯祲?愠摯敦渠潅捇慆牒挠楴湨潲浥慯?潩普?琷根攰?汴畯渠杭孥?嵨??楮??慥渷挹攰爨??椹??㈩ねふ???扴?????戼????????至?????????戰爱??嬼??崱′‵刼椯敢氾礨″????愠爵欴猵???倵愴漸?圼??刯?卛?洷畝琠愠瑓楯潤湡猠?椬湃?湯潩渠?獌洬慅汮汯?捯整汯氠?氬甼湩朾?捴愠湡捬攼爯孩?崮??楥?側物潦捩?乡慴瑩汯??捯慦搠?卨捥椠?啲?卮????業????ぅ???戭????扦?????㈠で???????扮牯??孳??嵬???敥敬?吠???敧攠????呥獲潛畊?圮???楎?整瑵?慥氼??椾???‰渷攬眼?挾礴琴漸琼漯硢椾挨?愠朱攵渳琩?昵父漱洭‵猶漶氮椼摢?猯琾慛琱攸?映攠牋海敡湫琠故摌?洠祂捡敮汧椠留浊?漠晃??楩??湥琠牄潒搬椠愼?挾慥浴瀠桡潬爼愯瑩愾??楁?孡?嵬??楴?偣氠慬湹瑭慰??敭摡??楩???づ????扩?????扮???????????????????扬牵??嬠??嵮??桲瑛瑊灝???眾睎眠?慮湧穬栠畊漠橍楥慤渼?捩漾洬?氰椱猰琬?慢猾瀳?猳椼搯?????戩爺??嬶代?崭??匷愰琳琮氼敢牲????愹獝椠渠慓?剡?删敁摔搬祙?????楙?敍瑩?慯氭??楮??味桯敮?牍漬氼敩 ̄潥晴?瑡桬攼?捩??敃瑬?灮慩瑣桡睬愠祦?楡湴?汲略湳朠?据慤渠捯敵牴?慯湭摥?瑯桦攠?灡潴瑩敥湮瑴楳愠汷?晴潨爠?瑯慮爭杳敭瑡敬摬?瑣桥敬牬愠灬祵孮?崠??楮?呥桲攠牷??搠癨??敢摯?传湅捍潌水??楌???そ????扊????扮??????????????戹爬??嬾??崼???用渲猶栩椺?丠???攭愴礠′匵???楢?夯???椰?攠琠?慨污??楁????剭儠?????慫?湧潡癷敡氠?愬渼摩 ̄獥整氠敡捬琼椯癩放?楃湲桩楺扯楴瑩潮物?漠晶?瑲桳敵?栠畣浨慥湭?捴??敲瑡?特攠捩敮瀠瑡潤牶?瑮祣牥潤猠楁湌敋?歰楯湳慩獴敩?睥椠瑬桵?慧渠瑣楡瑮畣浥潲牛?慝挮琼楩瘾楎琠祅孮?嵬??椠??潤氼??愾測挲攰爱″听格敢爾??椸????ㄨ???戺????戵??????????????????手牡??孹??嵡??匬敓煨畡楷猠瑁??噋?癡潮渠?偍愬眼敩氾????慬爼洯敩社?????楡?敩瑳?慳氠??椠??剱慵湩摲潥浤椠穣敲摩?灯桴慩獮敩????獳瑩畳摴祡?潣晥?敩牮氠潁瑌楋渭楲扥?灲汲畡獮?瑥楤瘠慬湵瑮楧渠楣扡?癣敥牲獳畛獊?攮爼汩漾瑓楣湩椠扔?灡汮畳獬?灍汥慤挼支扩漾?椲渰?瀲爬攼癢椾漴甼猯汢社?琱爲攰愩琺攱搲‰湲潡渱?献洼慢汲氯?捛攲氲汝?氠畓湡杫?捭慯湴捯攠版嬬?嵔??楫????汨楩渠?伬渠捈潩汲??楨????????扩?????扬?????????????‰?????扳牥??季??嵶???楌测??剮??楢浩?????慡湰条??剥??楦?敢瑬?慣汫??楧???楥戠牲潥扳汩慳獴瑡?杴爠潧睡瑴桥?晥慥捰瑥潲爠?牵整捡敮灴瑛潊牝???朾敃湡敮?慥浲瀠汣楥晬楬挼愯瑩椾漬渲‰椱猱?愼獢猾漱挹椼愯瑢放搨‵眩椺琶样?瀭漶漹爰?猼畢牲瘯椾癛愲氳?愠渠摋?捴楡杹慡牭敡琠瑒攬?獨浡潮欠楔湍本?摥潮獥慳朠敃?椼湩 ̄灥慴琠楡敬渼琯獩 ̄眮楔瑨桥?牡数獥敵捴瑩散搠?獴煲畡慴浥潧畩獥?挠整汯氠?汶略湲杣?捭慥渠捣敲物孺?嵴??楩????汳楩湳?佡湮捣潥氠??椠????????扬?????戠??????????????扡牲??孲??嵧??坨敥搠杦敵?卩副??敯湮摣牯敧睥????敍湌渴攭煁界楋湛?????椾?敲瑯?愠汎??楬???婡?㈠????慕?桓椠杁格氯祩 ̄瀬漲琰攱渱琬?潢爾愱氰永礼?扢椾漨愱瘸愩椺氷愠戵氳攵?瘷愠猵挴田氮愼牢?支渾摛漲琴桝攠氠楍慡汲?杩牬潪睥琠桔?昬慐捥瑩漠牗?牃敨捥敮瀠瑂漬爼?资?瑴礠牡潬猼椯湩放?歓楹湮慴獨敥?楩湳栬楳扴楲瑵潣牴?晲潥爭?瑣桴敩?瑩牴敹愠瑲浥敬湡瑴?潯普?捨慩湰捳攬牡孮?崠??椾??愠湶捩敶牯?刯敩猾??楦???ちっ???扦?????扮???ぬ????????????び??扥牣??孶??嵡??剰敬湡桳潴睩散?偬??偰敨捯捭桡椠?卩?卡桳慥昨敁牌?????楩?敩瑴?慲氠??楣???敲獯椭朼湩?獎琼爯畩挾琠甲爭攨?愭捩瑳楯癰楲瑯祰?牸敹氭愵琭業潥湴獨桹楬瀭猴?愨湰摩??楲?楤湩?瘭椴瘭潹???楨?据桹慬爩愭挼瑩放牎椼稯慩琾椠漴渭?漲昭???慯浰楲湯潰???扵敬湦穯楮浹楬搩慰穨潥汮???祰汹桲祩摭物潤煩畮楥渭漲氬椴渭???潭湩敮獥?慌?湋漳瘷攸氩?捵汲慲獥獮?漀昀?爀攀挀攀瀀琀漀爀?琀礀爀漀猀椀渀攀?欀椀渀愀猀攀?椀渀栀椀戀椀琀漀爀猀嬀?崀??椀????攀搀??栀攀洀??椀???  ???戀?????戀??????????????戀爀??嬀??崀??倀愀椀欀?倀???愀猀愀渀漀瘀椀挀???圀愀渀最????椀?攀琀?愀氀??椀???甀氀琀椀瀀氀攀砀?琀攀猀琀椀渀最?昀漀爀?搀爀椀瘀攀爀?洀甀琀愀琀椀漀渀猀?椀渀?猀焀甀愀洀漀甀猀?挀攀氀氀?挀愀爀挀椀渀漀洀愀猀?漀昀?琀栀攀?氀甀渀最嬀?崀??椀????氀椀渀?伀渀挀漀氀??椀??? ????戀?? ??戀????开猀甀瀀瀀氀????? ???戀爀??嬀??崀???甀爀最攀爀??吀?倀攀挀挀栀椀?匀?圀愀最洀愀渀????椀?攀琀?愀氀??椀???搀攀渀琀椀昀椀挀愀琀椀漀渀?漀昀?一嘀倀?????? ?愀猀?愀?瀀漀琀攀渀琀?猀攀氀攀挀琀椀瘀攀?漀爀愀氀氀礀?戀椀漀愀瘀愀椀氀愀戀氀攀?挀氀愀猀猀???倀???欀椀渀愀猀攀?椀渀栀椀戀椀琀漀爀?昀漀爀?琀爀攀愀琀椀渀最?挀愀渀挀攀爀嬀?崀??椀???匀??攀搀??栀攀洀??攀琀琀??椀??? ????戀????戀??? ???????????戀爀??嬀??崀???漀氀欀攀猀?????栀洀愀搀椀????氀搀攀爀琀漀渀?圀???椀?攀琀?愀氀??椀??吀栀攀?椀搀攀渀琀椀昀椀挀愀琀椀漀渀?漀昀??????椀????椀???渀搀愀稀漀氀???礀氀???????洀攀琀栀愀渀攀猀甀氀昀漀渀礀氀?瀀椀瀀攀爀愀稀椀渀???礀氀洀攀琀栀礀氀????洀漀爀瀀栀漀氀椀渀???礀氀?琀栀椀攀渀漀嬀????搀崀?瀀礀爀椀洀椀搀椀渀攀????? ????愀猀?愀?瀀漀琀攀渀琀?猀攀氀攀挀琀椀瘀攀?漀爀愀氀氀礀?戀椀漀愀瘀愀椀氀愀戀氀攀?椀渀栀椀戀椀琀漀爀?漀昀?挀氀愀猀猀???倀???欀椀渀愀猀攀?昀漀爀?琀栀攀?琀爀攀愀琀洀攀渀琀?漀昀?挀愀渀挀攀爀嬀?崀??椀????攀搀??栀攀洀??椀???  ???戀?????戀???????????????????戀爀??嬀??崀??倀愀椀欀?倀????爀挀椀氀愀??????愀爀愀?????椀?攀琀?愀氀??椀????氀椀渀椀挀愀氀?挀栀愀爀愀挀琀攀爀椀猀琀椀挀猀?漀昀?瀀愀琀椀攀渀琀猀?眀椀琀栀?氀甀渀最?愀搀攀渀漀挀愀爀挀椀渀漀洀愀猀?栀愀爀戀漀爀椀渀最??刀???洀甀琀愀琀椀漀渀猀嬀?崀??椀????氀椀渀?伀渀挀漀氀??椀??? ????戀?????戀???????? ????? ????戀爀??嬀??崀??刀栀攀愀甀氀琀?吀刀?匀琀攀氀氀眀愀最攀渀?????搀樀愀戀攀渀最?????椀?攀琀?愀氀??椀???椀猀挀漀瘀攀爀礀?漀昀?搀愀戀爀愀昀攀渀椀戀?愀?猀攀氀攀挀琀椀瘀攀?椀渀栀椀戀椀琀漀爀?漀昀?刀愀昀?欀椀渀愀猀攀猀?眀椀琀栀?愀渀琀椀琀甀洀漀爀?愀挀琀椀瘀椀琀礀?愀最愀椀渀猀琀???刀愀昀?搀爀椀瘀攀渀?琀甀洀漀爀猀嬀?崀??椀???匀??攀搀??栀攀洀??攀琀琀??椀??? ????戀????戀??????????????戀爀??嬀? 崀???爀漀戀?吀???愀渀渀攀渀最椀攀猀猀攀爀???吀猀漀甀爀氀愀欀椀猀?????椀?攀琀?愀氀??椀???攀琀攀爀漀最攀渀攀椀琀礀?漀昀??刀????愀洀瀀氀椀昀椀挀愀琀椀漀渀?椀渀?愀搀攀渀漀挀愀爀挀椀渀漀洀愀?猀焀甀愀洀漀甀猀?挀攀氀氀?挀愀爀挀椀渀漀洀愀?愀渀搀?氀愀爀最攀?挀攀氀氀?甀渀搀椀昀昀攀爀攀渀琀椀愀琀攀搀?挀愀爀挀椀渀漀洀愀?漀昀?琀栀攀?氀甀渀最嬀?崀??椀??漀搀?倀愀琀栀漀氀??椀??? ????戀?????戀???????????????????戀爀??嬀??崀??匀栀椀洀愀洀甀爀愀?吀??椀????椀渀愀洀椀?夀??椀?攀琀?愀氀??椀??一漀渀?猀洀愀氀氀?挀攀氀氀?氀甀渀最?挀愀渀挀攀爀?愀渀搀??愀????琀爀愀渀猀昀漀爀洀攀搀?挀攀氀氀猀?栀愀爀戀漀爀椀渀最?琀栀攀??刀????????椀渀猀嘀开????洀甀琀愀琀椀漀渀?愀爀攀?猀攀渀猀椀琀椀瘀攀?琀漀?琀栀攀?搀甀愀氀?猀瀀攀挀椀昀椀挀?攀瀀椀搀攀爀洀愀氀?最爀漀眀琀栀?昀愀挀琀漀爀?爀攀挀攀瀀琀漀爀?愀渀搀??刀????椀渀栀椀戀椀琀漀爀????????嬀?崀??椀??愀渀挀攀爀?刀攀猀??椀???  ???戀?????戀???????????????????戀爀??嬀??崀???愀渀搀栀椀????愀栀氀攀搀愀?刀??氀攀愀爀礀?????椀?攀琀?愀氀??椀??吀眀漀?搀椀洀攀渀猀椀漀渀愀氀?瀀栀愀猀攀???猀琀甀搀礀?漀昀?渀攀爀愀琀椀渀椀戀?一?刀?挀漀洀戀椀渀攀搀?眀椀琀栀?琀攀洀猀椀爀漀氀椀洀甀猀?吀???椀渀?瀀愀琀椀攀渀琀猀?倀琀猀?眀椀琀栀?猀漀氀椀搀?琀甀洀漀爀猀嬀?崀??椀????氀椀渀?伀渀挀漀氀??椀??? ????戀?????戀?????匀甀瀀瀀氀???? ????戀爀??嬀??崀???攀??爀攀瘀攀???吀攀甀最攀氀猀????攀攀爀猀????椀?攀琀?愀氀??椀???氀椀渀椀挀愀氀?愀挀琀椀瘀椀琀礀?漀昀?愀昀愀琀椀渀椀戀????圀??????椀渀?瀀愀琀椀攀渀琀猀?眀椀琀栀?氀甀渀最?愀搀攀渀漀挀愀爀挀椀渀漀洀愀?眀椀琀栀?洀甀琀愀琀椀漀渀猀?椀渀?琀栀攀?欀椀渀愀猀攀?搀漀洀愀椀渀?漀昀???刀??渀攀甀嬀?崀??椀??甀渀最??愀渀挀攀爀??椀??? ????戀?????戀??????????????戀爀??嬀??崀???愀洀洀攀爀洀愀渀?倀匀?匀漀猀????刀愀洀漀猀?????椀?攀琀?愀氀??椀???甀琀愀琀椀漀渀猀?椀渀?琀栀攀???刀??欀椀渀愀猀攀?最攀渀攀?椀搀攀渀琀椀昀礀?愀?渀漀瘀攀氀?琀栀攀爀愀瀀攀甀琀椀挀?琀愀爀最攀琀?椀渀?猀焀甀愀洀漀甀猀?挀攀氀氀?氀甀渀最?挀愀渀挀攀爀嬀?崀??椀??愀渀挀攀爀??椀猀挀漀瘀??椀??? ????戀????戀????????????戀爀??嬀??崀???愀礀???圀愀琀攀爀猀???匀瀀椀攀最攀氀????椀?攀琀?愀氀??椀???渀栀椀戀椀琀椀漀渀?漀昀?挀漀氀氀愀最攀渀?椀渀搀甀挀攀搀?搀椀猀挀漀椀搀椀渀?搀漀洀愀椀渀?爀攀挀攀瀀琀漀爀???愀渀搀???愀挀琀椀瘀愀琀椀漀渀?戀礀?椀洀愀琀椀渀椀戀?渀椀氀漀琀椀渀椀戀?愀渀搀?搀愀猀愀琀椀渀椀戀嬀?崀??椀??甀爀???倀栀愀爀洀愀挀漀氀??椀???  ???戀??????戀????????????????戀爀??嬀??崀???漀栀渀猀漀渀?????攀欀攀氀攀??一??攀渀最????椀?攀琀?愀氀??椀??倀栀愀猀攀????猀琀甀搀礀?漀昀?搀愀猀愀琀椀渀椀戀?椀渀?瀀愀琀椀攀渀琀猀?眀椀琀栀?愀搀瘀愀渀挀攀搀?渀漀渀?猀洀愀氀氀?挀攀氀氀?氀甀渀最?挀愀渀挀攀爀嬀?崀??椀????氀椀渀?伀渀挀漀氀??椀??? ? ??戀?????戀??? ????? ????????
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