张波液体活检在肠癌精准医疗中的应用

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1、液体活检在肠癌精准医疗中的应用张波北京大学医学部病理学系GlobalandSpanishIdentifyingcodes:2015-06-POLN-9XPMA8;DateofApproval:02/07/15;2015-06-POLN-9XPMLD;DateofApproval:02/07/15Prescribinginformationisavailableonrequest结直肠癌的发生率和死亡率http://globocan.iarc.fr/Pages/fact_sheets_population.aspx19992000200120022003200420052006200720

2、082009201020112012卡培他滨单药美国依立替康(+5-FU+叶酸)依立替康(+5-FU+亚叶酸)奥沙利铂(+5-FU+亚叶酸)卡培他滨联合治疗BEV+氟嘧啶为基础的CTBEV+氟嘧啶为基础的CTBEV+CT西妥昔单抗+化疗(EGFR/KRAS野生型)帕尼单抗+FOLFOX(EGFR/KRAS野生型)欧盟奥沙利铂(+5-FU+亚叶酸)瑞戈非尼三/四线阿柏西普(二线)西妥昔单抗+FOLFIRI(KRAS野生型)BEV:贝伐单抗;CT:化疗;EGFR:表皮生长因子受体FU:氟尿嘧啶;KRAS:克尔斯滕大鼠肉瘤病毒癌基因同源物西妥昔单抗+化疗(EGFR/RAS野生型)2014

3、无分子标记物KRAS标记物RAS标记物mCRC治疗方案的更新-从KRAS到RAS分子标记物的发展史Metastaticcolorectalcancerpatienttriagetoanti-EGFRtreatmentinclinicalpractice结直肠癌分子靶向治疗相关检测瑞格菲尼西妥昔/帕尼单抗Aspirin结直肠癌分子检测概略IHC:MMRLynchsyndrome预防：LS；治疗：5-FU；预后：MSI；靶向治疗；预后K-RAS突变KRASmutationsinvariouscancertypesKRASrecurrentmutationsincancersKRAS突变在原发

4、及转移结肠癌灶K-RAS基因突变检测Cetuximab(西妥昔)andpanitumumab(帕尼)aremonoclonalantibodiesthatbindtotheextracellulardomainofEGFR,therebyinhibitingdownstreamsignalingandresultingindecreasedcellproliferationandmigration.K-RASforpredictingresponsetoanti-EGFRantibodies,cetuximaborpanitumumab.codons12oftheK-RASgenealm

5、ostneverbenefitedfromtreatmentwiththeseantibodies.However,15–20%ofpatientswithwild-typeK-RASshowanobjectiveresponsewithantibodyaloneand35–40%,whentreatedwithcetuximabandirinotecan.G13Dmaybeanexception.administrationofcetuximabtopatientswiththismutationwasassociatedwithasignificantlybetteroutcomet

6、hanthatseeninpatientswithothertypesofK-RASmutations.Anti-epidermalgrowthfactorreceptor(EGFR)treatmentofMetastaticcolorectalcancer(mCRC)patients瑞格菲尼西妥昔/帕尼单抗KRAS基因突变检测的意义KRAS基因突变与anti-EGFR靶向治疗：G13D例外：需进一步证实；However,codon12and13mutationsmaydifferintermsoftheirclinicalimpact.Indeed,evidencederivedret

7、rospectivelyinasmallcohort(n=32)ofchemotherapy-refractorymCRCpatientssuggeststhatpatientswithtumorsharboringG13Dmutations(thethirdmostfrequentKRASmutationinCRC)maybenefitfromanti-EGFRantibodytherapy.KRAS基因突变的预后意义；KRAS检