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1、,單擊此處編輯母版標題樣式,單擊此處編輯母版文本樣式,第二級,第三級,第四級,第五級,單擊此處編輯母版標題樣式,單擊此處編輯母版文本樣式,第二級,第三級,第四級,第五級,基于藥物基因組學(xué),的,非,小細胞肺癌精準醫(yī)療,疾病的病因、發(fā)生與發(fā)展,疾病,預(yù)防,疾病,診斷,疾病治療,健康管理,基因檢測的意義,與基因的相關(guān)性,疾病發(fā)生,藥物治療,Alzheimer,老年癡呆,Cancer,腫瘤,30%,25%,=Drug does not work,藥物無效,Anti-Depressants,抗抑郁,Asthma,哮喘,Diabetes,糖尿病,Arthritis,關(guān)節(jié)炎,62%,60%,57%,50%,
2、Drug,藥物,Efficacy,藥效,如何篩選對藥物有效的人群？,如何實施個性化的治療？,臨床藥物與療效,Trends Mol,Med.2001;7(5,):201-4,藥物,代謝與藥物的作用,CYP2C19,基因多態(tài)性與藥物療效,Genet,Med.2017;19(2,):215-223.,藥物代謝及反應(yīng)受到多種因素影響,藥,物,反應(yīng),個體,差異,年,齡,老,年,、,兒童,、,新生兒,性,別,身,高,、體,重,環(huán),境,因素,食,物,/,吸,煙,/,合,并,用藥,合并,癥,病,程,器,官,功能,基因型,遺傳因素（基因）,藥物有毒性,但有效,藥物有毒性,且無效,藥物無毒性且有效,藥物無毒性也無
3、效,同種同量,藥物治療,疾病臨床癥狀與,基因的關(guān)系,臨床癥狀,精準醫(yī)療,內(nèi)在因素,外,在因素,組織器官損傷,基因變異,生活習(xí)慣,環(huán)境因素,藥物相互作用,食物,表觀遺傳,基因修飾,精準,醫(yī)療與基因變異,內(nèi)憂外患,基因多態(tài)性,轉(zhuǎn)運,蛋白異常,代謝,酶異常,受體異常,吸收,分布,排泄,代謝,藥物,效應(yīng)異常,血藥濃度差異,藥物療效和毒性的個體差異,藥物個體差異的評價策略,臨床療效,藥物蓄積,蛋白質(zhì),DNA,或,RNA,傳統(tǒng)治療方式,未來,醫(yī)學(xué)模式,診斷,用藥方案,治療,監(jiān)控反應(yīng),調(diào)整方案,診斷,基因,分析,用藥方案,治療,安全有效,合理的個體化用藥,傳統(tǒng)治療,傳統(tǒng)醫(yī)療模式向個體化治療轉(zhuǎn)化,個體化治療,
4、不良反應(yīng)少,療效好,省錢,省時,分層治療,因人而異,基于藥物基因組的臨床,用藥,指南,https:/cpicpgx.org/,https:/www.pharmvar.org/,https,:/www.pharmgkb.org,/,https,:/www.clinicalgenome.org/,https:/,www.fda.gov/drugs/science-and-research-drugs/table-pharmacogenomic-biomarkers-drug-labeling,.,基于藥物基因組的臨床用藥分類,J Pers,Med.2021;11(3,):210,Mutat Res
5、.2008;642(1-2):1-13.,腫瘤本質(zhì)上是一種基因病，是內(nèi)因與環(huán)境因素相互作用的結(jié)局,腫瘤精,準,醫(yī)療,的,依據(jù),腫瘤發(fā)病機制,變異來源,生殖細胞,腫瘤細胞,藥物治療方式,常規(guī)化療,靶,向治療,臨床藥物遺傳學(xué),聯(lián)盟（,CPIC,）,藥物,基因,指南,藥物,基因,指南,abacavir,HLA-B,guideline,paroxetine,CYP2D6,guideline,allopurinol,HLA-B,guideline,peginterferon,IFNL3,guideline,amitriptyline,CYP2C19/D6,guideline,phenytoin,CYP2
6、C9/HLA-B,guideline,atazanavir,UGT1A1,guideline,rasburicase,G6PD,guideline,azathioprine,TPMT,guideline,sertraline,CYP2C19,guideline,capecitabine,DPYD,guideline,simvastatin,SLCO1B1,guideline,carbamazepine,HLA-B,guideline,tacrolimus,CYP3A5,guideline,citalopram,CYP2C19,guideline,tamoxifen,CYP2D6,guideli
7、ne,clomipramine,CYP2C19/2D6,guideline,tegafur,DPYD,guideline,clopidogrel,CYP2C19,guideline,thioguanine,TPMT,guideline,codeine,CYP2D6,guideline,trimipramine,CYP2C19/2D6,guideline,desipramine,CYP2D6,guideline,tropisetron,CYP2D6,guideline,CPIC,腫瘤,藥物基因應(yīng)用指南,Genetic Marker,Application,Drug,BCR-ABL,Ph+CML;
8、Ph+ALL,Imatinib,dasatinib,nilotinib,BCR-ABL/T315I,Resistance to anti-BCR-ABL agents,Imatinib,dasatinib,nilotinib,BRAF V600E,Metastatic melanoma,Vemurafenib,BRCA1/2,Metastatic ovarian cancer and breast cancer with BRCA 1/2 mutations,Olaparib,veliparib,iniparib,KIT,Kit(CD117)-positive malignant GIST,I
9、matinib,EGFR,Locally advanced,unresectable,or metastatic NSCLC,Erlotinib,gefitinib,EGFR T790M,Resistance to EGFR tyrosine kinase inhibitors in advanced NSCLC,Erlotinib,gefitinib,EML4-ALK,ALK kinase inhibitor for metastatic NSCLC with this fusion gene,Crizotinib,HER2 amplification,HER2-positive breas
10、t cancer or metastatic gastric or gastroesophageal junction adenocarcinoma,Trastuzumab,KRAS,Resistance to EGFR antibodies in metastatic colorectal cancer,Cetuximab,panitumumab,PML/RAR,Acute promyelocytic leukemia,ATRA,arsenic trioxide,TPMT,Deficiency is associated with increased risk of myelotoxicit
11、y,Mercaptopurine,zathioprine,UGT1A1,Homozygosity for UGT1A1,28 is associated with risk of toxicity,Irinotecan,來源于美國,FDA,網(wǎng)站,FDA,藥物基因標記與臨床用藥,FDA,腫瘤,藥物基因應(yīng)用指南,非小細胞肺癌,常見抗腫瘤,藥物,Abraxane(Paclitaxel Albumin-stabilized Nanoparticle Formulation),Paclitaxel Albumin-stabilized Nanoparticle Formulation,Gilotrif(
12、Afatinib Dimaleate),Mekinist(Trametinib Dimethyl Sulfoxide),Doxorubicin Hydrochloride,Gemzar(Gemcitabine Hydrochloride),Tepmetko(Tepotinib Hydrochloride),Afatinib Dimaleate,Pemetrexed Disodium,Gefitinib,MethotrexateSodium,Durvalumab,Ceritinib,Tepotinib Hydrochloride,Afinitor(Everolimus),Portrazza(Ne
13、citumumab),Pralsetinib,Mvasi(Bevacizumab),Entrectinib,Crizotinib,Pembrolizumab,Afinitor Disperz(Everolimus),TrametinibDimethyl Sulfoxide,Gemcitabine Hydrochloride,Keytruda(Pembrolizumab),Erlotinib Hydrochloride,Cyramza(Ramucirumab),Trexall(Methotrexate Sodium),Alecensa(Alectinib),Ramucirumab,Gavreto
14、(Pralsetinib),Cemiplimab-rwlc,Everolimus,Dabrafenib Mesylate,Vizimpro(Dacomitinib),Alectinib,Retevmo(Selpercatinib),Imfinzi(Durvalumab),Opdivo(Nivolumab),Dacomitinib,Tarceva(Erlotinib Hydrochloride),Vinorelbine Tartrate,Alimta(Pemetrexed Disodium),Rozlytrek(Entrectinib),Infugem(Gemcitabine Hydrochlo
15、ride),Osimertinib Mesylate,Docetaxel,Taxotere(Docetaxel),Zirabev(Bevacizumab),Alunbrig(Brigatinib),Selpercatinib,Ipilimumab,Paclitaxel,Brigatinib,Carboplatin,Zykadia(Ceritinib),GEMCITABINE-CISPLATIN,Tabrecta(Capmatinib Hydrochloride),Paraplatin(Carboplatin),Libtayo(Cemiplimab-rwlc),Capmatinib Hydroc
16、hloride,Paraplat(Carboplatin),Tagrisso(Osimertinib Mesylate),Avastin(Bevacizumab),Tafinlar(Dabrafenib Mesylate),Yervoy(Ipilimumab),Lorbrena(Lorlatinib),Necitumumab,Atezolizumab,Tecentriq(Atezolizumab),Bevacizumab,CARBOPLATIN-TAXOL,Iressa(Gefitinib),Lorlatinib,Nivolumab,Xalkori(Crizotinib),非小細胞肺癌藥物選擇與基因檢測相關(guān)臨床診療指南,Non-Small Cell Lung Cancer(Version 4.2021 March 3,2021,),非小細胞肺癌藥物選擇與基因檢測相關(guān)臨床診療指南,Non-Small Cell Lung Cancer(Version 4.2021 March 3,2021,),非小細胞肺癌藥物選擇與基因檢測相關(guān)臨床診療指南,（,2021,韓國共識聲明：非小細胞肺癌分子生物
基于藥物基因組學(xué)的非小細胞肺癌精準醫(yī)療課件
