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NLCC2020حMETͨ·ǰ·ڣ

2020-6-20 20:45| : С| 鿴: 50| : 2|ԭ: С

ժҪ: 2020ȫΰᣨNLCC6.20-6.21¡ؿĻδߵֱʽУڶרҡѧ߲뵽˴δᵱСݷḻܽ㱨˽ΰоչ йMETеоܴ ...
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2020ȫΰᣨNLCC6.20-6.21¡ؿĻδߵֱʽУڶרҡѧ߲뵽˴δᵱСݷḻܽ㱨˽ΰоչ

йMETеоܴĿMETеݷ꣬жݺҩʽMETеķΰȫٴӦá

ʹҷһ»пƼѧͬҽѧԺͬҽԺٻڴġMETͨ·ڷΰƵ½չо档

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NGS⼼ķչҩIJзĿǰΰİѾȡ˳ĽչγӴİϵMETҩϵзչѸ٣ΪҪưе㡣
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ڷΰMETе쳣ҲжԡMET 14ӵԾͻ3%-4%ķΰг֣ǷҪ²ռ20%-31.8%ͻ䣬MET׵ĹXзΰоɷ֣ռȸߴ25%-75%METڳλиߴ2%-4%ͬʱһEGFR-TKIҩļ̷ԭռ5%-21%һTKIҩߣռ15%-30%

ٻڴMETṹźͨ·METźͨ·쳣METԷСϸΰƽչ棬ΪȫMETео
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1

METṹźͨ·

MET ȫƤתӣϳɵĵ c-MET ǿϸӣHGFϵһҰἤøHGF Ŀǰֵ c-MET Ψһ壬ҪڼϸҲɱϸͨԷڻƷáHGF c-MET Sema ʹ c-MET ۻữε׵Ұлڶźͨ· PI3K-AktRas-MAPKSTAT Wnt/-catenin ȣӶϸֳϸϸǨơϮѪܼѪɵЧӦ֯չзӹؼác-MET ͨ·ʱٽ֯ķֻ޸쳣ʱٽϸֳתơ
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METźͨ·쳣

METͨ·쳣ʽΪ͵档ϣ֣MET14ӵԾͻ䡢౶塢METײϣΪMET׵Ĺ
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²ϣMETȿԭ°ҲΪEGFR-TKIҩļ̷ءǰΪMETMET14ԾͻͬʱΪ°أҪMET
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MET׵ĸ߱оH-ַǸMetmab׼жϵٴַڼооδЧءɸѡܹMETƼлİƻߡĿǰٴʵУIHCc-MET׹ΪMET쳣ͷΰijɸѡԻ߿ԣٴҽIHCc-METữˮƽFISHMETǷȡ
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Ӽⷽʽ˵METļ⣬ԲӫⶨPCRFISHַFISHжϱ׼CappuzzoϵͳPathVysionϵͳPathVysionҪǿFISHмMETλĿΪյCEP7λĿжMET򿽱MET gene copies number, MET GCN׼棺һMET/CEP7ıֵڶÿһϸĻ򿽱ϸռϸ
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ع˼ٴоMETļⷽҪFISHNGS⣬ֲñȽϻӽ(comparative genome hybridization,CGH)
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MET14ͻļⷽNGSһοȫͻʽʶձӦá
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METͨ·ĸ쳣вͬļⷽMET黯׷㣬ܳΪҩݣʾܣɲFISHһȷNGSΪMETһѡ񡣵TATTONоʾо߲˲ͬķMETͨ47߽METһоͬʱʹNGSIHCFISHMETͬʱΪԵĸΪ21%򷨵Ϊ26%FISHⷨʿɸߴ47%ɴ˿ɼ򷨶METļԽϲNGSת¼PCRMET14ͻҪѡ÷ⷽƣٴϿѡá
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3

METԷСϸΰƽչ

ĿǰȫѾжMETƼлзСûƻ֣METƼԱΪࣺ

1ATPԵСcMETƼIͺII͡IƼҪϼøڴڴATPU͹Met1211ףγɽʽΪIaͺIbͣIaһǷеƼMETЧܽҩ᣻IbƼֻMETøMETЧǿҩᡢ沴IIƼԽϴATPλ㵽CIle1145 ףڶּøлԣҩǿᡣ

2ATPǾСcMETƣҩTivantinibARQ197ARQ197һַATP͵ c-METữƼ øķữи߶ȵѡԡTivantinibжϹؼ߻л໥áTivantinibĽṹc-MetøϵӣΪƼ԰󶨲ͬڼļøṹһ๹󣬸ǿcMET

3MET/HGFĵ¡壬OnartuzumabһԴĵ¡壬METϣMETHGF໥ãMETͨ·ĻӶƵɵη¼ij֡
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HGF/c-MET źͨ·λIJֿͬɽMETİҩΪHGF ¡塢 c-MET ¡СƼ 3 ࡣ

HGF¡塢 c-MET¡ֱ HGF c-MET ϣӶֹ HGF c-METĽϼữֹźŴСƼҪָ c-MET ҰἤøƼĤڼø򣬴ӶֹữźŴҰἤøƼֿɷΪѡԺͷе࣬ѡƼҪ c-METеƼڰ c-MET ڵĶҰἤø塣

˽ҩƻһMETƼٴӦ̽켣һʼMETƼڷѡԵķΰȺоTivantinib϶NSCLCûлóɹоǽMETƼתMETͨ·쳣ѡԷΰȺ˳ĽϣҩMETȱﻼߣֳЧȼǶMETƼٴϣйMETƼҩоҲ

MET14ͻٴо

1

ڽ2020ASCOϣ˹MET14ͻķͷСϸΰIIٴоʾЧΪ49.2%

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оı֮˸߱ķ35.7%תƻߣ24.3%ȺԤ󶼽ϲͬҩоδйսЧȻܱͬˮƽMET14ͻΰľЧԡ
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DCRߴ95%PFSߴ9.7¡
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2沴

2020ASCOͬ沴MET14ͻķΰVISIONٴоЧΪ45%λPFSΪ8.5


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3

ϰ깫һMETƼǿGEOMETRY MONO-1ооø飬14ͻоУƳλεMET14ͻΰλЧΪ67.9%PFS9.7£λЧΪ49.6% PFSֻ5.4
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GEOMETRY MONO-1о̽˿METȺGCN10ЧԣڳMETȺЧΪ40%λOSΪ9.56£5aھMETȺЧΪ29%λOSΪ10.61£1a
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ۺϱȽĸоԿDCRPFSԼתƱĸоߵģͬʱûмԷ׵ķȫԸ
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METٴо

METȻҲΪMETƼõİе㣬Ƕо֤ʵˮƽMETٴЧܱ֤ڵ͡С߲ͬˮƽȺЧȫֱͬΪ014%40%ζſֻMET/CEP7ˮƽߵĻвһЧڵˮƽĻмûЧ
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TATTONоУEGFR-TKI+TKIҩ䷢METĻߣʾ1/2EGFR-TKIҩ󣬶ԾMETT790MͻĻ߲ðϣ80mg QD+ 300mg QDƣЧΪ64%PFSΪ9.1£PartD;1/2EGFR-TKIҩ󣬶ԾT790MͻMETĻߣðϣ80mg QD+600mgƣЧΪ67%PFSΪ11.0£PartB33EGFR-TKIҩ󣬶METĻߣ96%ڶ߼ϰϣչ52%ϲתƵ£ðϣ80mg QD+600mgƣЧΪ30%PFSΪ5.4£PartB1
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ϼEGFR TKIҩMETĻߣȺп+ORR 29%, λPFSֻ5.5


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沴ϼȺ沴+ vs +˳/=4.9 vs 4.4£PFSORRûͳѧ졣EGFR TKIҩ黯MET2+3+ /ISHMET(GCN5/MET/CEP-7ȡ2) ķΰߣЧΪΪ45.2%Ըڶջ33.3%黯3+ȺУЧʸߴ68.4%MET飬Чʸߴ66.7%ҲչʾˮƽЧԡ
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METƼҩԭٴ̽

˶ԲͬMET쳣ʽٴֵ̽⣬ҩ࣬ȫҲ̽METƼҩļ̷ԭ򡣱2017Clinical cancer research־Ϸһƪ£ʾMWET124H8METD1246NͻǵMETƼҩԭ
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ٻܽᵽMETͻIJͬʽڳηΰEGFR-TKIҩΰжӦռȡŸҩо֤METƼڷΰӦý봺졣
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ղ
ȫ(2)
Ҿͷ 2020-6-23 14:38
ʲôʱУм۸񣬶ҽЩҲϵŻ
ס999 2020-7-2 18:23
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