{ "c": { "sampleId": 60406928, "sampleSn": "/", "barcode": "2023WSSW000709-T", "name": "刘杰", "agentName": "上海清港泉生物科技有限公司", "hospitalName": "/", "testDoctor": "/", "itemName": "LZ118.新80基因组织版", "itemNum": 1, "sampleStatus": "YWC", "contact": "", "source": "蜡块", "makeTime": "2023-03-21 00:00:00", "receiveTime": "2023-03-25", "reportTime": "2023-07-31", "remark": "留样本，实验后转寄", "idCard": "", "lockStatus": 0, "waringTime": "0000-00-00 00:00:00", "division": "/", "zlType": "/", "familySn": "/", "estimateEndTime": "0000-00-00 00:00:00", "doctorUserId": 0, "areaAgentId": 1253, "agentId": 2008, "unitAgentId": 2007, "labId": 0, "orderType": "/", "receiveStatus": 1, "sampleInfoId": 94338196, "gender": "女", "age": 57, "contactAddr": "/", "familyRel": "/", "birthday": "/", "treatmentNo": "/", "treatHistory": "/", "sickFamilyHistory": "/", "treatResult": "结肠癌" }, "snvindel": [ { "gene": "APC", "transcript": "NM_000038", "exon": "exon16", "nacid": "c.4156A>T", "aacid": "p.R1386X", "mutant_frequency": "26.4%", "AMP_mut_level": "III", "muttype": "提前终止", "Gene_function": ".", "drug_category": {}, "drug_content": [], "alter": "APC:NM_000038:exon16:c.4156A>T:p.R1386X" }, { "gene": "EGFR", "transcript": "NM_005228", "exon": "exon12", "nacid": "c.1352G>A", "aacid": "p.R451H", "mutant_frequency": "1.33%", "AMP_mut_level": "III", "muttype": "错义突变", "Gene_function": ".", "drug_category": {}, "drug_content": [], "alter": "EGFR:NM_005228:exon12:c.1352G>A:p.R451H" }, { "gene": "EGFR", "transcript": "NM_005228", "exon": "exon17", "nacid": "c.1994G>A", "aacid": "p.G665D", "mutant_frequency": "1.01%", "AMP_mut_level": "III", "muttype": "错义突变", "Gene_function": ".", "drug_category": {}, "drug_content": [], "alter": "EGFR:NM_005228:exon17:c.1994G>A:p.G665D" }, { "gene": "EGFR", "transcript": "NM_005228", "exon": "exon28", "nacid": "c.3508C>T", "aacid": "p.P1170S", "mutant_frequency": "1.37%", "AMP_mut_level": "III", "muttype": "错义突变", "Gene_function": ".", "drug_category": {}, "drug_content": [], "alter": "EGFR:NM_005228:exon28:c.3508C>T:p.P1170S" }, { "gene": "EGFR", "transcript": "NM_201283", "exon": "exon10", "nacid": "c.1213A>G", "aacid": "p.S405G", "mutant_frequency": "1.09%", "AMP_mut_level": "III", "muttype": "错义突变", "Gene_function": ".", "drug_category": {}, "drug_content": [], "alter": "EGFR:NM_201283:exon10:c.1213A>G:p.S405G" }, { "gene": "FGFR3", "transcript": "NM_000142", "exon": "exon6", "nacid": "c.670G>A", "aacid": "p.G224S", "mutant_frequency": "1.82%", "AMP_mut_level": "III", "muttype": "错义突变", "Gene_function": ".", "drug_category": {}, "drug_content": [], "alter": "FGFR3:NM_000142:exon6:c.670G>A:p.G224S" }, { "gene": "KRAS", "transcript": "NM_004985", "exon": "exon2", "nacid": "c.35G>T", "aacid": "p.G12V", "mutant_frequency": "22.18%", "AMP_mut_level": "II", "muttype": "错义突变", "Gene_function": "KRAS是小分子GTP酶RAS家族的成员，该家族催化GTP水解为GDP。在生理条件下，这些RAS蛋白在活性(GTP结合)和非活性(GDP结合)状态间循环，以激活受体酪氨酸激酶(RTK)下游的MAPK和PI3K致癌途径信号传导(PMID: 22189424)。RAS酶的功能受到鸟嘌呤核苷酸交换因子(GEF)如SOS的调节，这些因子可以使GDP与GTP交换，也可以通过GTP酶活化蛋白如NF1调节，提高RAS水解GTP的能力。一旦被激活，RAS可通过激活不同的细胞内信号传导途径(包括RAF/MEK/ERK和PI3K/AKT/mTOR途径)介导细胞增殖和其他细胞功能的调节。", "drug_category": { "c": "考比替尼 + Ipatasertib 【C 级】\n贝美替尼 【C 级】\n曲美替尼 【D 级】\nRMC-6236 【D 级】", "d": "西妥昔单抗 【C 级】\n曲妥珠单抗 + 妥卡替尼 【C 级】\n帕尼单抗 【C 级】\n曲妥珠单抗 + 帕妥珠单抗,曲妥珠单抗 + 拉帕替尼,trastuzumab deruxtecan 【C 级】\nEGFR-TKI 【C 级】" }, "drug_content": [ { "index": 0, "DrugCn": "西妥昔单抗", "Response_Type": "耐药", "Indication": "结直肠癌", "Evidence_Source": "FDA", "Efficacy_Evidence": "Cetuximab是一种表皮生长因子受体(EGFR)拮抗剂，FDA指出Cetuximab不适用于RAS突变型或RAS突变情况未知的结直肠癌患者(FDA-approval: 11/2020)。" }, { "index": 1, "DrugCn": "曲妥珠单抗 + 妥卡替尼", "Response_Type": "耐药", "Indication": "结直肠癌", "Evidence_Source": "FDA", "Efficacy_Evidence": "FDA推荐Trastuzumab + Tucatinib应用于携带HER2重复，RAS野生型的结直肠癌患者(NCCN: Rectal Cancer-Version 4.2022)" }, { "index": 2, "DrugCn": "帕尼单抗", "Response_Type": "耐药", "Indication": "结直肠癌", "Evidence_Source": "FDA", "Efficacy_Evidence": "Panitumumab是一种表皮生长因子受体(EGFR)拮抗剂，FDA指出Panitumumab不适用于RAS突变型或RAS突变状态未知的转移性结直肠癌患者(FDA-approval: 06/2017)。" }, { "index": 3, "DrugCn": "曲妥珠单抗 + 帕妥珠单抗,曲妥珠单抗 + 拉帕替尼,trastuzumab deruxtecan", "Response_Type": "耐药", "Indication": "结直肠癌", "Evidence_Source": "NCCN", "Efficacy_Evidence": "NCCN指南指出携带KRAS突变的结直肠癌患者对trastuzumab + pertuzumab,trastuzumab + lapatinib,trastuzumab deruxtecan治疗不敏感(NCCN: Colon Cancer-Version 2.2021)。" }, { "index": 4, "DrugCn": "EGFR-TKI", "Response_Type": "耐药", "Indication": "非小细胞肺癌", "Evidence_Source": "NCCN", "Efficacy_Evidence": "NCCN指南指出携带KRAS、BRAF基因突变和ALK、ROS1融合的非小细胞肺癌患者可能对EGFR信号通路抑制剂类靶向药物耐药(NCCN: Non-Small Cell Lung Cancer-Version 6.2021)。" }, { "index": 5, "DrugCn": "考比替尼 + Ipatasertib", "Response_Type": "可能敏感", "Indication": "实体瘤", "Evidence_Source": "临床试验", "Efficacy_Evidence": "在一项Ib期临床试验中，13例携带KRAS突变的晚期实体瘤肿瘤患者接受Cobimetinib+ipatasertib联合治疗后，2例部分缓解，3例病情稳定，6例疾病进展为最佳反应(PMID: 32737717)。" }, { "index": 6, "DrugCn": "贝美替尼", "Response_Type": "可能敏感", "Indication": "实体瘤", "Evidence_Source": "临床试验", "Efficacy_Evidence": "在一项I期临床试验中，纳入21位晚期实体瘤患者接受Binimetinib治疗，其中8例患者携带KRAS突变。在纳入分析的18例患者中，14例患者病情稳定，包含4例携带KRAS突变患者(PMID: 27071922)。" }, { "index": 7, "DrugCn": "曲美替尼", "Response_Type": "可能敏感", "Indication": "实体瘤", "Evidence_Source": "临床前研究", "Efficacy_Evidence": "在一项临床前研究中，曲美替尼可抑制BRAF V600E和KRAS突变肿瘤细胞系的增殖，其IC50值低于PD0325901或selumetinib，虽然曲美替尼和PD0325901在体外对MEK1具有相似的效力。与PD0325901相比，在这些浓度下用曲美替尼或CH5126766处理48小时，可在KRAS突变细胞(H2030)和表达活性CRAF数量增加的A375细胞中更持久地抑制pERK活性(PMID: 24746704)。" }, { "index": 8, "DrugCn": "RMC-6236", "Response_Type": "可能敏感", "Indication": "实体瘤", "Evidence_Source": "临床前研究", "Efficacy_Evidence": "在体外实验中，RMC-6236抑制了细胞生长，并诱导多种RAS癌细胞株凋亡，在临床前体内异种移植模型中，RMC-6236可抑制RAS通路的激活长达48小时。与健康组织相比RMC-6236对肿瘤组织的亲和力更高，在多种细胞系来源的异种移植模型（NSCLC、CRC和PDAC等）中RMC-6236对KRAS突变（特别是KRAS G12D, KRAS G12V和 KRAS G12R）均有明显也持久的肿瘤消退效果（Abstract: Koltun et al. Abstract# 3597, AACR 2022）。" } ], "alter": "KRAS:NM_004985:exon2:c.35G>T:p.G12V" }, { "gene": "NF1", "transcript": "NM_000267", "exon": "exon38", "nacid": "c.5694G>C", "aacid": "p.E1898D", "mutant_frequency": "1.07%", "AMP_mut_level": "III", "muttype": "错义突变", "Gene_function": ".", "drug_category": {}, "drug_content": [], "alter": "NF1:NM_000267:exon38:c.5694G>C:p.E1898D" }, { "gene": "PIK3CA", "transcript": "NM_006218", "exon": "exon10", "nacid": "c.1636C>A", "aacid": "p.Q546K", "mutant_frequency": "2.4%", "AMP_mut_level": "II", "muttype": "错义突变", "Gene_function": "PIK3CA基因编码磷脂酰肌醇3-激酶(PI3K)的p110α催化亚基，PI3K是由受体酪氨酸激酶 [例如表皮生长因子受体(EGFR)和人表皮生长受体2 (HER2/ERBB2)] 驱动的信号转导通路中的整合信号分子。PI3K的活性形式由调节性p85亚单位和催化性p110亚单位组成。激活的PI3K将PIP2转化为PIP3，引发AKT(蛋白激酶B)的磷酸化和雷帕霉素(mTOR)激酶的激活。PI3K/AKT/mTOR信号通路通过调节各种细胞功能(包括细胞增殖、存活、代谢和细胞骨架重组)来促进肿瘤发生(PMID: 16453012)。", "drug_category": { "c": "阿培利司 【C 级】\nRLY-2608 【D 级】" }, "drug_content": [ { "index": 9, "DrugCn": "阿培利司", "Response_Type": "可能敏感", "Indication": "实体瘤", "Evidence_Source": "临床I期", "Efficacy_Evidence": "在一项I期临床试验中，携带PIK3CA基因突变的晚期实体瘤患者当使用Alpelisib (BYL719)治疗后，58.2% (78/134)的患者病情得到控制，1个患者获得完全缓解，7个部分缓解，70个患者疾病稳定，临床受益率 (CR+PR+SD>24 weeks)为15.7% (21/134)(PMID: 29401002; NCT01219699)。" }, { "index": 10, "DrugCn": "RLY-2608", "Response_Type": "可能敏感", "Indication": "实体瘤", "Evidence_Source": "临床I期", "Efficacy_Evidence": "RLY-2608是一种新型PI3Kα抑制剂，一项I期临床研究旨在评估RLY-2608作为单药在PI3KCA突变的晚期实体瘤患者以及与氟维司群联合用于PIK3CA突变，HR+，HER2-转移性乳腺癌（MBC）的中的临床活性。实验正在进行中（Abstract: Perez et al. Abstract# TPS1124, ASCO 2022）。" } ], "alter": "PIK3CA:NM_006218:exon10:c.1636C>A:p.Q546K" }, { "gene": "RET", "transcript": "NM_020975", "exon": "exon2", "nacid": "c.220G>A", "aacid": "p.G74S", "mutant_frequency": "1.24%", "AMP_mut_level": "III", "muttype": "错义突变", "Gene_function": ".", "drug_category": {}, "drug_content": [], "alter": "RET:NM_020975:exon2:c.220G>A:p.G74S" }, { "gene": "TP53", "transcript": "NM_000546", "exon": "exon4", "nacid": "c.216dupC", "aacid": "p.V73Rfs*76", "mutant_frequency": "27.53%", "AMP_mut_level": "II", "muttype": "移码突变", "Gene_function": "TP53编码p53肿瘤抑制蛋白，这是一种转录因子，通过诱导下游抗肿瘤反应，如DNA损伤修复和凋亡，对细胞应激(包括DNA损伤和致癌性激活)产生应答(PMID: 11099028)。p53蛋白由一个N末端反式激活结构域，一个中心DNA结合结构域、一个寡聚结构域，以及一个C末端调节结构域组成(PMID: 22713868)。", "drug_category": { "c": "培唑帕尼 + 伏立诺他 【C 级】\n贝伐珠单抗 【C 级】" }, "drug_content": [ { "index": 11, "DrugCn": "培唑帕尼 + 伏立诺他", "Response_Type": "可能敏感", "Indication": "实体瘤", "Evidence_Source": "临床I期", "Efficacy_Evidence": "在一项I期试验中，Votrient（培唑帕尼）和Zolinza（伏立诺他）的联合疗法改善了携带TP53热点突变的晚期实体瘤患者的无进展生存期和总生存率，疾病稳定率为45％（5/11），而未检测到TP53突变患者的疾病稳定率为16％（4/25）（PMID：25669829）。" }, { "index": 12, "DrugCn": "贝伐珠单抗", "Response_Type": "可能敏感", "Indication": "实体瘤", "Evidence_Source": "临床试验", "Efficacy_Evidence": "在一项临床试验中，106位携带TP53突变的晚期实体瘤患者使用VEGF/VEGFR抑制剂如Bevacizumab治疗，其疾病稳定、部分缓解、完全缓解、总生存期、从开始治疗到治疗失败的时间这些指标均好于TP53基因野生型的82位患者(PMID: 27466356)。在一项回顾性研究中，携带TP53基因突变的癌症患者采用bevacizumab治疗，其疾病无进展生存期长于TP53基因野生型患者(PMID: 23670029)。" } ], "alter": "TP53:NM_000546:exon4:c.216dupC:p.V73Rfs*76" } ], "fusion": [], "cnv": [], "hotspot": [ { "Validated": 1, "Chr": "chr12", "Start": 25398284, "End": 25398284, "Ref": "C", "Alt": "A", "AAChange.refGene": "KRAS:NM_004985:exon2:c.35G>T:p.G12V", "mutant_frequency": 0.2234, "total_reads": 1817, "mutant_reads": 406, "strand_bias": "222:184", "Otherinfo10": "PASS", "Func.refGene": "exonic", "Gene.refGene": "KRAS", "ExonicFunc.refGene": "nonsynonymous SNV", "avsnp150": "rs121913529", "cosmic91": "ID=COSV55497419;OCCURENCE=20(breast),1(female_genital_tract_(site_indeterminate)),7(liver),36(peritoneum),9(genital_tract),7(oesophagus),24(cervix),5668(large_intestine),1(central_nervous_system),189(biliary_tract),2(pleura),1(vulva),341(ovary),20(NS),45(stomach),90(haematopoietic_and_lymphoid_tissue),8(kidney),9(soft_tissue),32(urinary_tract),2142(pancreas),1(autonomic_ganglia),11(gastrointestinal_tract_(site_indeterminate)),30(skin),42(prostate),1579(lung),25(thyroid),5(upper_aerodigestive_tract),24(testis),4(thymus),1(eye),42(small_intestine),165(endometrium)", "CLNDN": "Acute_myeloid_leukemia|Cerebral_arteriovenous_malformation|Nevus_sebaceous|Juvenile_myelomonocytic_leukemia|Non-small_cell_lung_carcinoma|Neoplasm_of_the_thyroid_gland|Neoplasm_of_ovary|Neoplasm_of_the_large_intestine|Carcinoma_of_pancreas|not_provided", "CLNSIG": "Pathogenic", "ACMG_level": 1, "Deleterious": 2, "freq_high": 0, "OKBSIG": "Oncogenic", "AMP_evidence_level": "A", "AMP_mut_level": "I", "Indication": "结直肠癌", "DrugCn": "西妥昔单抗", "Response_Type": "耐药", "Evidence_Source": "FDA", "Efficacy_Evidence": "Cetuximab是一种表皮生长因子受体(EGFR)拮抗剂，FDA指出Cetuximab不适用于RAS突变型或RAS突变情况未知的结直肠癌患者(FDA-approval: 11/2020)。", "Gene_function": "KRAS是小分子GTP酶RAS家族的成员，该家族催化GTP水解为GDP。在生理条件下，这些RAS蛋白在活性(GTP结合)和非活性(GDP结合)状态间循环，以激活受体酪氨酸激酶(RTK)下游的MAPK和PI3K致癌途径信号传导(PMID: 22189424)。RAS酶的功能受到鸟嘌呤核苷酸交换因子(GEF)如SOS的调节，这些因子可以使GDP与GTP交换，也可以通过GTP酶活化蛋白如NF1调节，提高RAS水解GTP的能力。一旦被激活，RAS可通过激活不同的细胞内信号传导途径(包括RAF/MEK/ERK和PI3K/AKT/mTOR途径)介导细胞增殖和其他细胞功能的调节。", "Drug_Category": "d", "Otherinfo11": "SAMPLE=2023WSSW000709-T;TYPE=SNV;DP=1817;VD=406;AF=0.2234;BIAS=2:2;REFBIAS=742:665;VARBIAS=222:184;PMEAN=39.5;PSTD=1;QUAL=34;QSTD=1;SBF=0.4986;ODDRATIO=1.08124472893195;MQ=60;SN=44.111;HIAF=0.2215;ADJAF=0.0083;SHIFT3=0;MSI=2;MSILEN=1;NM=1.2;HICNT=397;HICOV=1792;LSEQ=AGGCACTCTTGCCTACGCCA;RSEQ=CAGCTCCAACTACCACAAGT;DUPRATE=0;SPLITREAD=0;SPANPAIR=0", "Otherinfo12": "GT:DP:VD:AD:AF:RD:ALD", "Otherinfo13": "0/1:1817:406:1407,406:0.2234:742,665:222,184" }, { "Validated": 1, "Chr": "chr12", "Start": 25398284, "End": 25398284, "Ref": "C", "Alt": "A", "AAChange.refGene": "KRAS:NM_004985:exon2:c.35G>T:p.G12V", "mutant_frequency": 0.2234, "total_reads": 1817, "mutant_reads": 406, "strand_bias": "222:184", "Otherinfo10": "PASS", "Func.refGene": "exonic", "Gene.refGene": "KRAS", "ExonicFunc.refGene": "nonsynonymous SNV", "avsnp150": "rs121913529", "cosmic91": "ID=COSV55497419;OCCURENCE=20(breast),1(female_genital_tract_(site_indeterminate)),7(liver),36(peritoneum),9(genital_tract),7(oesophagus),24(cervix),5668(large_intestine),1(central_nervous_system),189(biliary_tract),2(pleura),1(vulva),341(ovary),20(NS),45(stomach),90(haematopoietic_and_lymphoid_tissue),8(kidney),9(soft_tissue),32(urinary_tract),2142(pancreas),1(autonomic_ganglia),11(gastrointestinal_tract_(site_indeterminate)),30(skin),42(prostate),1579(lung),25(thyroid),5(upper_aerodigestive_tract),24(testis),4(thymus),1(eye),42(small_intestine),165(endometrium)", "CLNDN": "Acute_myeloid_leukemia|Cerebral_arteriovenous_malformation|Nevus_sebaceous|Juvenile_myelomonocytic_leukemia|Non-small_cell_lung_carcinoma|Neoplasm_of_the_thyroid_gland|Neoplasm_of_ovary|Neoplasm_of_the_large_intestine|Carcinoma_of_pancreas|not_provided", "CLNSIG": "Pathogenic", "ACMG_level": 1, "Deleterious": 2, "freq_high": 0, "OKBSIG": "Oncogenic", "AMP_evidence_level": "A", "AMP_mut_level": "I", "Indication": "结直肠癌", "DrugCn": "曲妥珠单抗 + 妥卡替尼", "Response_Type": "耐药", "Evidence_Source": "FDA", "Efficacy_Evidence": "FDA推荐Trastuzumab + Tucatinib应用于携带HER2重复，RAS野生型的结直肠癌患者(NCCN: Rectal Cancer-Version 4.2022)", "Gene_function": "KRAS是小分子GTP酶RAS家族的成员，该家族催化GTP水解为GDP。在生理条件下，这些RAS蛋白在活性(GTP结合)和非活性(GDP结合)状态间循环，以激活受体酪氨酸激酶(RTK)下游的MAPK和PI3K致癌途径信号传导(PMID: 22189424)。RAS酶的功能受到鸟嘌呤核苷酸交换因子(GEF)如SOS的调节，这些因子可以使GDP与GTP交换，也可以通过GTP酶活化蛋白如NF1调节，提高RAS水解GTP的能力。一旦被激活，RAS可通过激活不同的细胞内信号传导途径(包括RAF/MEK/ERK和PI3K/AKT/mTOR途径)介导细胞增殖和其他细胞功能的调节。", "Drug_Category": "d", "Otherinfo11": "SAMPLE=2023WSSW000709-T;TYPE=SNV;DP=1817;VD=406;AF=0.2234;BIAS=2:2;REFBIAS=742:665;VARBIAS=222:184;PMEAN=39.5;PSTD=1;QUAL=34;QSTD=1;SBF=0.4986;ODDRATIO=1.08124472893195;MQ=60;SN=44.111;HIAF=0.2215;ADJAF=0.0083;SHIFT3=0;MSI=2;MSILEN=1;NM=1.2;HICNT=397;HICOV=1792;LSEQ=AGGCACTCTTGCCTACGCCA;RSEQ=CAGCTCCAACTACCACAAGT;DUPRATE=0;SPLITREAD=0;SPANPAIR=0", "Otherinfo12": "GT:DP:VD:AD:AF:RD:ALD", "Otherinfo13": "0/1:1817:406:1407,406:0.2234:742,665:222,184" }, { "Validated": 1, "Chr": "chr12", "Start": 25398284, "End": 25398284, "Ref": "C", "Alt": "A", "AAChange.refGene": "KRAS:NM_004985:exon2:c.35G>T:p.G12V", "mutant_frequency": 0.2234, "total_reads": 1817, "mutant_reads": 406, "strand_bias": "222:184", "Otherinfo10": "PASS", "Func.refGene": "exonic", "Gene.refGene": "KRAS", "ExonicFunc.refGene": "nonsynonymous SNV", "avsnp150": "rs121913529", "cosmic91": "ID=COSV55497419;OCCURENCE=20(breast),1(female_genital_tract_(site_indeterminate)),7(liver),36(peritoneum),9(genital_tract),7(oesophagus),24(cervix),5668(large_intestine),1(central_nervous_system),189(biliary_tract),2(pleura),1(vulva),341(ovary),20(NS),45(stomach),90(haematopoietic_and_lymphoid_tissue),8(kidney),9(soft_tissue),32(urinary_tract),2142(pancreas),1(autonomic_ganglia),11(gastrointestinal_tract_(site_indeterminate)),30(skin),42(prostate),1579(lung),25(thyroid),5(upper_aerodigestive_tract),24(testis),4(thymus),1(eye),42(small_intestine),165(endometrium)", "CLNDN": "Acute_myeloid_leukemia|Cerebral_arteriovenous_malformation|Nevus_sebaceous|Juvenile_myelomonocytic_leukemia|Non-small_cell_lung_carcinoma|Neoplasm_of_the_thyroid_gland|Neoplasm_of_ovary|Neoplasm_of_the_large_intestine|Carcinoma_of_pancreas|not_provided", "CLNSIG": "Pathogenic", "ACMG_level": 1, "Deleterious": 2, "freq_high": 0, "OKBSIG": "Oncogenic", "AMP_evidence_level": "A", "AMP_mut_level": "I", "Indication": "结直肠癌", "DrugCn": "帕尼单抗", "Response_Type": "耐药", "Evidence_Source": "FDA", "Efficacy_Evidence": "Panitumumab是一种表皮生长因子受体(EGFR)拮抗剂，FDA指出Panitumumab不适用于RAS突变型或RAS突变状态未知的转移性结直肠癌患者(FDA-approval: 06/2017)。", "Gene_function": "KRAS是小分子GTP酶RAS家族的成员，该家族催化GTP水解为GDP。在生理条件下，这些RAS蛋白在活性(GTP结合)和非活性(GDP结合)状态间循环，以激活受体酪氨酸激酶(RTK)下游的MAPK和PI3K致癌途径信号传导(PMID: 22189424)。RAS酶的功能受到鸟嘌呤核苷酸交换因子(GEF)如SOS的调节，这些因子可以使GDP与GTP交换，也可以通过GTP酶活化蛋白如NF1调节，提高RAS水解GTP的能力。一旦被激活，RAS可通过激活不同的细胞内信号传导途径(包括RAF/MEK/ERK和PI3K/AKT/mTOR途径)介导细胞增殖和其他细胞功能的调节。", "Drug_Category": "d", "Otherinfo11": "SAMPLE=2023WSSW000709-T;TYPE=SNV;DP=1817;VD=406;AF=0.2234;BIAS=2:2;REFBIAS=742:665;VARBIAS=222:184;PMEAN=39.5;PSTD=1;QUAL=34;QSTD=1;SBF=0.4986;ODDRATIO=1.08124472893195;MQ=60;SN=44.111;HIAF=0.2215;ADJAF=0.0083;SHIFT3=0;MSI=2;MSILEN=1;NM=1.2;HICNT=397;HICOV=1792;LSEQ=AGGCACTCTTGCCTACGCCA;RSEQ=CAGCTCCAACTACCACAAGT;DUPRATE=0;SPLITREAD=0;SPANPAIR=0", "Otherinfo12": "GT:DP:VD:AD:AF:RD:ALD", "Otherinfo13": "0/1:1817:406:1407,406:0.2234:742,665:222,184" }, { "Validated": 1, "Chr": "chr12", "Start": 25398284, "End": 25398284, "Ref": "C", "Alt": "A", "AAChange.refGene": "KRAS:NM_004985:exon2:c.35G>T:p.G12V", "mutant_frequency": 0.2234, "total_reads": 1817, "mutant_reads": 406, "strand_bias": "222:184", "Otherinfo10": "PASS", "Func.refGene": "exonic", "Gene.refGene": "KRAS", "ExonicFunc.refGene": "nonsynonymous SNV", "avsnp150": "rs121913529", "cosmic91": "ID=COSV55497419;OCCURENCE=20(breast),1(female_genital_tract_(site_indeterminate)),7(liver),36(peritoneum),9(genital_tract),7(oesophagus),24(cervix),5668(large_intestine),1(central_nervous_system),189(biliary_tract),2(pleura),1(vulva),341(ovary),20(NS),45(stomach),90(haematopoietic_and_lymphoid_tissue),8(kidney),9(soft_tissue),32(urinary_tract),2142(pancreas),1(autonomic_ganglia),11(gastrointestinal_tract_(site_indeterminate)),30(skin),42(prostate),1579(lung),25(thyroid),5(upper_aerodigestive_tract),24(testis),4(thymus),1(eye),42(small_intestine),165(endometrium)", "CLNDN": "Acute_myeloid_leukemia|Cerebral_arteriovenous_malformation|Nevus_sebaceous|Juvenile_myelomonocytic_leukemia|Non-small_cell_lung_carcinoma|Neoplasm_of_the_thyroid_gland|Neoplasm_of_ovary|Neoplasm_of_the_large_intestine|Carcinoma_of_pancreas|not_provided", "CLNSIG": "Pathogenic", "ACMG_level": 1, "Deleterious": 2, "freq_high": 0, "OKBSIG": "Oncogenic", "AMP_evidence_level": "A", "AMP_mut_level": "I", "Indication": "结直肠癌", "DrugCn": "曲妥珠单抗 + 帕妥珠单抗,曲妥珠单抗 + 拉帕替尼,trastuzumab deruxtecan", "Response_Type": "耐药", "Evidence_Source": "NCCN", "Efficacy_Evidence": "NCCN指南指出携带KRAS突变的结直肠癌患者对trastuzumab + pertuzumab,trastuzumab + lapatinib,trastuzumab deruxtecan治疗不敏感(NCCN: Colon Cancer-Version 2.2021)。", "Gene_function": "KRAS是小分子GTP酶RAS家族的成员，该家族催化GTP水解为GDP。在生理条件下，这些RAS蛋白在活性(GTP结合)和非活性(GDP结合)状态间循环，以激活受体酪氨酸激酶(RTK)下游的MAPK和PI3K致癌途径信号传导(PMID: 22189424)。RAS酶的功能受到鸟嘌呤核苷酸交换因子(GEF)如SOS的调节，这些因子可以使GDP与GTP交换，也可以通过GTP酶活化蛋白如NF1调节，提高RAS水解GTP的能力。一旦被激活，RAS可通过激活不同的细胞内信号传导途径(包括RAF/MEK/ERK和PI3K/AKT/mTOR途径)介导细胞增殖和其他细胞功能的调节。", "Drug_Category": "d", "Otherinfo11": "SAMPLE=2023WSSW000709-T;TYPE=SNV;DP=1817;VD=406;AF=0.2234;BIAS=2:2;REFBIAS=742:665;VARBIAS=222:184;PMEAN=39.5;PSTD=1;QUAL=34;QSTD=1;SBF=0.4986;ODDRATIO=1.08124472893195;MQ=60;SN=44.111;HIAF=0.2215;ADJAF=0.0083;SHIFT3=0;MSI=2;MSILEN=1;NM=1.2;HICNT=397;HICOV=1792;LSEQ=AGGCACTCTTGCCTACGCCA;RSEQ=CAGCTCCAACTACCACAAGT;DUPRATE=0;SPLITREAD=0;SPANPAIR=0", "Otherinfo12": "GT:DP:VD:AD:AF:RD:ALD", "Otherinfo13": "0/1:1817:406:1407,406:0.2234:742,665:222,184" }, { "Validated": 1, "Chr": "chr12", "Start": 25398284, "End": 25398284, "Ref": "C", "Alt": "A", "AAChange.refGene": "KRAS:NM_004985:exon2:c.35G>T:p.G12V", "mutant_frequency": 0.2234, "total_reads": 1817, "mutant_reads": 406, "strand_bias": "222:184", "Otherinfo10": "PASS", "Func.refGene": "exonic", "Gene.refGene": "KRAS", "ExonicFunc.refGene": "nonsynonymous SNV", "avsnp150": "rs121913529", "cosmic91": "ID=COSV55497419;OCCURENCE=20(breast),1(female_genital_tract_(site_indeterminate)),7(liver),36(peritoneum),9(genital_tract),7(oesophagus),24(cervix),5668(large_intestine),1(central_nervous_system),189(biliary_tract),2(pleura),1(vulva),341(ovary),20(NS),45(stomach),90(haematopoietic_and_lymphoid_tissue),8(kidney),9(soft_tissue),32(urinary_tract),2142(pancreas),1(autonomic_ganglia),11(gastrointestinal_tract_(site_indeterminate)),30(skin),42(prostate),1579(lung),25(thyroid),5(upper_aerodigestive_tract),24(testis),4(thymus),1(eye),42(small_intestine),165(endometrium)", "CLNDN": "Acute_myeloid_leukemia|Cerebral_arteriovenous_malformation|Nevus_sebaceous|Juvenile_myelomonocytic_leukemia|Non-small_cell_lung_carcinoma|Neoplasm_of_the_thyroid_gland|Neoplasm_of_ovary|Neoplasm_of_the_large_intestine|Carcinoma_of_pancreas|not_provided", "CLNSIG": "Pathogenic", "ACMG_level": 1, "Deleterious": 2, "freq_high": 0, "OKBSIG": "Oncogenic", "AMP_evidence_level": "C", "AMP_mut_level": "II", "Indication": "非小细胞肺癌", "DrugCn": "EGFR-TKI", "Response_Type": "耐药", "Evidence_Source": "NCCN", "Efficacy_Evidence": "NCCN指南指出携带KRAS、BRAF基因突变和ALK、ROS1融合的非小细胞肺癌患者可能对EGFR信号通路抑制剂类靶向药物耐药(NCCN: Non-Small Cell Lung Cancer-Version 6.2021)。", "Gene_function": "KRAS是小分子GTP酶RAS家族的成员，该家族催化GTP水解为GDP。在生理条件下，这些RAS蛋白在活性(GTP结合)和非活性(GDP结合)状态间循环，以激活受体酪氨酸激酶(RTK)下游的MAPK和PI3K致癌途径信号传导(PMID: 22189424)。RAS酶的功能受到鸟嘌呤核苷酸交换因子(GEF)如SOS的调节，这些因子可以使GDP与GTP交换，也可以通过GTP酶活化蛋白如NF1调节，提高RAS水解GTP的能力。一旦被激活，RAS可通过激活不同的细胞内信号传导途径(包括RAF/MEK/ERK和PI3K/AKT/mTOR途径)介导细胞增殖和其他细胞功能的调节。", "Drug_Category": "d", "Otherinfo11": "SAMPLE=2023WSSW000709-T;TYPE=SNV;DP=1817;VD=406;AF=0.2234;BIAS=2:2;REFBIAS=742:665;VARBIAS=222:184;PMEAN=39.5;PSTD=1;QUAL=34;QSTD=1;SBF=0.4986;ODDRATIO=1.08124472893195;MQ=60;SN=44.111;HIAF=0.2215;ADJAF=0.0083;SHIFT3=0;MSI=2;MSILEN=1;NM=1.2;HICNT=397;HICOV=1792;LSEQ=AGGCACTCTTGCCTACGCCA;RSEQ=CAGCTCCAACTACCACAAGT;DUPRATE=0;SPLITREAD=0;SPANPAIR=0", "Otherinfo12": "GT:DP:VD:AD:AF:RD:ALD", "Otherinfo13": "0/1:1817:406:1407,406:0.2234:742,665:222,184" }, { "Validated": 1, "Chr": "chr12", "Start": 25398284, "End": 25398284, "Ref": "C", "Alt": "A", "AAChange.refGene": "KRAS:NM_004985:exon2:c.35G>T:p.G12V", "mutant_frequency": 0.2234, "total_reads": 1817, "mutant_reads": 406, "strand_bias": "222:184", "Otherinfo10": "PASS", "Func.refGene": "exonic", "Gene.refGene": "KRAS", "ExonicFunc.refGene": "nonsynonymous SNV", "avsnp150": "rs121913529", "cosmic91": "ID=COSV55497419;OCCURENCE=20(breast),1(female_genital_tract_(site_indeterminate)),7(liver),36(peritoneum),9(genital_tract),7(oesophagus),24(cervix),5668(large_intestine),1(central_nervous_system),189(biliary_tract),2(pleura),1(vulva),341(ovary),20(NS),45(stomach),90(haematopoietic_and_lymphoid_tissue),8(kidney),9(soft_tissue),32(urinary_tract),2142(pancreas),1(autonomic_ganglia),11(gastrointestinal_tract_(site_indeterminate)),30(skin),42(prostate),1579(lung),25(thyroid),5(upper_aerodigestive_tract),24(testis),4(thymus),1(eye),42(small_intestine),165(endometrium)", "CLNDN": "Acute_myeloid_leukemia|Cerebral_arteriovenous_malformation|Nevus_sebaceous|Juvenile_myelomonocytic_leukemia|Non-small_cell_lung_carcinoma|Neoplasm_of_the_thyroid_gland|Neoplasm_of_ovary|Neoplasm_of_the_large_intestine|Carcinoma_of_pancreas|not_provided", "CLNSIG": "Pathogenic", "ACMG_level": 1, "Deleterious": 2, "freq_high": 0, "OKBSIG": "Oncogenic", "AMP_evidence_level": "B", "AMP_mut_level": "I", "Indication": "结直肠癌", "DrugCn": "Irinotecan + 司美替尼", "Response_Type": "可能敏感", "Evidence_Source": "临床II期", "Efficacy_Evidence": "在一项II期临床研究中，Selumetinib (AZD6244)联合Camptosar (伊立替康)导致9.7% (3/31)携带KRAS外显子2突变的结直肠癌患者部分反应，51.6% (16/31)患者病情稳定(PMID: 25322874)。", "Gene_function": "KRAS是小分子GTP酶RAS家族的成员，该家族催化GTP水解为GDP。在生理条件下，这些RAS蛋白在活性(GTP结合)和非活性(GDP结合)状态间循环，以激活受体酪氨酸激酶(RTK)下游的MAPK和PI3K致癌途径信号传导(PMID: 22189424)。RAS酶的功能受到鸟嘌呤核苷酸交换因子(GEF)如SOS的调节，这些因子可以使GDP与GTP交换，也可以通过GTP酶活化蛋白如NF1调节，提高RAS水解GTP的能力。一旦被激活，RAS可通过激活不同的细胞内信号传导途径(包括RAF/MEK/ERK和PI3K/AKT/mTOR途径)介导细胞增殖和其他细胞功能的调节。", "Drug_Category": "c", "Otherinfo11": "SAMPLE=2023WSSW000709-T;TYPE=SNV;DP=1817;VD=406;AF=0.2234;BIAS=2:2;REFBIAS=742:665;VARBIAS=222:184;PMEAN=39.5;PSTD=1;QUAL=34;QSTD=1;SBF=0.4986;ODDRATIO=1.08124472893195;MQ=60;SN=44.111;HIAF=0.2215;ADJAF=0.0083;SHIFT3=0;MSI=2;MSILEN=1;NM=1.2;HICNT=397;HICOV=1792;LSEQ=AGGCACTCTTGCCTACGCCA;RSEQ=CAGCTCCAACTACCACAAGT;DUPRATE=0;SPLITREAD=0;SPANPAIR=0", "Otherinfo12": "GT:DP:VD:AD:AF:RD:ALD", "Otherinfo13": "0/1:1817:406:1407,406:0.2234:742,665:222,184" }, { "Validated": 1, "Chr": "chr12", "Start": 25398284, "End": 25398284, "Ref": "C", "Alt": "A", "AAChange.refGene": "KRAS:NM_004985:exon2:c.35G>T:p.G12V", "mutant_frequency": 0.2234, "total_reads": 1817, "mutant_reads": 406, "strand_bias": "222:184", "Otherinfo10": "PASS", "Func.refGene": "exonic", "Gene.refGene": "KRAS", "ExonicFunc.refGene": "nonsynonymous SNV", "avsnp150": "rs121913529", "cosmic91": "ID=COSV55497419;OCCURENCE=20(breast),1(female_genital_tract_(site_indeterminate)),7(liver),36(peritoneum),9(genital_tract),7(oesophagus),24(cervix),5668(large_intestine),1(central_nervous_system),189(biliary_tract),2(pleura),1(vulva),341(ovary),20(NS),45(stomach),90(haematopoietic_and_lymphoid_tissue),8(kidney),9(soft_tissue),32(urinary_tract),2142(pancreas),1(autonomic_ganglia),11(gastrointestinal_tract_(site_indeterminate)),30(skin),42(prostate),1579(lung),25(thyroid),5(upper_aerodigestive_tract),24(testis),4(thymus),1(eye),42(small_intestine),165(endometrium)", "CLNDN": "Acute_myeloid_leukemia|Cerebral_arteriovenous_malformation|Nevus_sebaceous|Juvenile_myelomonocytic_leukemia|Non-small_cell_lung_carcinoma|Neoplasm_of_the_thyroid_gland|Neoplasm_of_ovary|Neoplasm_of_the_large_intestine|Carcinoma_of_pancreas|not_provided", "CLNSIG": "Pathogenic", "ACMG_level": 1, "Deleterious": 2, "freq_high": 0, "OKBSIG": "Oncogenic", "AMP_evidence_level": "C", "AMP_mut_level": "II", "Indication": "结直肠癌", "DrugCn": "曲美替尼", "Response_Type": "可能敏感", "Evidence_Source": "临床I期", "Efficacy_Evidence": "在一项I期临床试验中，8名患有结肠直肠癌的患者中包含3名携带KRAS突变的患者，在使用Mekinist（曲美替尼）治疗疾病稳定（PMID:22805291）。", "Gene_function": "KRAS是小分子GTP酶RAS家族的成员，该家族催化GTP水解为GDP。在生理条件下，这些RAS蛋白在活性(GTP结合)和非活性(GDP结合)状态间循环，以激活受体酪氨酸激酶(RTK)下游的MAPK和PI3K致癌途径信号传导(PMID: 22189424)。RAS酶的功能受到鸟嘌呤核苷酸交换因子(GEF)如SOS的调节，这些因子可以使GDP与GTP交换，也可以通过GTP酶活化蛋白如NF1调节，提高RAS水解GTP的能力。一旦被激活，RAS可通过激活不同的细胞内信号传导途径(包括RAF/MEK/ERK和PI3K/AKT/mTOR途径)介导细胞增殖和其他细胞功能的调节。", "Drug_Category": "c", "Otherinfo11": "SAMPLE=2023WSSW000709-T;TYPE=SNV;DP=1817;VD=406;AF=0.2234;BIAS=2:2;REFBIAS=742:665;VARBIAS=222:184;PMEAN=39.5;PSTD=1;QUAL=34;QSTD=1;SBF=0.4986;ODDRATIO=1.08124472893195;MQ=60;SN=44.111;HIAF=0.2215;ADJAF=0.0083;SHIFT3=0;MSI=2;MSILEN=1;NM=1.2;HICNT=397;HICOV=1792;LSEQ=AGGCACTCTTGCCTACGCCA;RSEQ=CAGCTCCAACTACCACAAGT;DUPRATE=0;SPLITREAD=0;SPANPAIR=0", "Otherinfo12": "GT:DP:VD:AD:AF:RD:ALD", "Otherinfo13": "0/1:1817:406:1407,406:0.2234:742,665:222,184" }, { "Validated": 1, "Chr": "chr12", "Start": 25398284, "End": 25398284, "Ref": "C", "Alt": "A", "AAChange.refGene": "KRAS:NM_004985:exon2:c.35G>T:p.G12V", "mutant_frequency": 0.2234, "total_reads": 1817, "mutant_reads": 406, "strand_bias": "222:184", "Otherinfo10": "PASS", "Func.refGene": "exonic", "Gene.refGene": "KRAS", "ExonicFunc.refGene": "nonsynonymous SNV", "avsnp150": "rs121913529", "cosmic91": "ID=COSV55497419;OCCURENCE=20(breast),1(female_genital_tract_(site_indeterminate)),7(liver),36(peritoneum),9(genital_tract),7(oesophagus),24(cervix),5668(large_intestine),1(central_nervous_system),189(biliary_tract),2(pleura),1(vulva),341(ovary),20(NS),45(stomach),90(haematopoietic_and_lymphoid_tissue),8(kidney),9(soft_tissue),32(urinary_tract),2142(pancreas),1(autonomic_ganglia),11(gastrointestinal_tract_(site_indeterminate)),30(skin),42(prostate),1579(lung),25(thyroid),5(upper_aerodigestive_tract),24(testis),4(thymus),1(eye),42(small_intestine),165(endometrium)", "CLNDN": "Acute_myeloid_leukemia|Cerebral_arteriovenous_malformation|Nevus_sebaceous|Juvenile_myelomonocytic_leukemia|Non-small_cell_lung_carcinoma|Neoplasm_of_the_thyroid_gland|Neoplasm_of_ovary|Neoplasm_of_the_large_intestine|Carcinoma_of_pancreas|not_provided", "CLNSIG": "Pathogenic", "ACMG_level": 1, "Deleterious": 2, "freq_high": 0, "OKBSIG": "Oncogenic", "AMP_evidence_level": "C", "AMP_mut_level": "II", "Indication": "实体瘤", "DrugCn": "考比替尼 + Ipatasertib", "Response_Type": "可能敏感", "Evidence_Source": "临床试验", "Efficacy_Evidence": "在一项Ib期临床试验中，13例携带KRAS突变的晚期实体瘤肿瘤患者接受Cobimetinib+ipatasertib联合治疗后，2例部分缓解，3例病情稳定，6例疾病进展为最佳反应(PMID: 32737717)。", "Gene_function": "KRAS是小分子GTP酶RAS家族的成员，该家族催化GTP水解为GDP。在生理条件下，这些RAS蛋白在活性(GTP结合)和非活性(GDP结合)状态间循环，以激活受体酪氨酸激酶(RTK)下游的MAPK和PI3K致癌途径信号传导(PMID: 22189424)。RAS酶的功能受到鸟嘌呤核苷酸交换因子(GEF)如SOS的调节，这些因子可以使GDP与GTP交换，也可以通过GTP酶活化蛋白如NF1调节，提高RAS水解GTP的能力。一旦被激活，RAS可通过激活不同的细胞内信号传导途径(包括RAF/MEK/ERK和PI3K/AKT/mTOR途径)介导细胞增殖和其他细胞功能的调节。", "Drug_Category": "c", "Otherinfo11": "SAMPLE=2023WSSW000709-T;TYPE=SNV;DP=1817;VD=406;AF=0.2234;BIAS=2:2;REFBIAS=742:665;VARBIAS=222:184;PMEAN=39.5;PSTD=1;QUAL=34;QSTD=1;SBF=0.4986;ODDRATIO=1.08124472893195;MQ=60;SN=44.111;HIAF=0.2215;ADJAF=0.0083;SHIFT3=0;MSI=2;MSILEN=1;NM=1.2;HICNT=397;HICOV=1792;LSEQ=AGGCACTCTTGCCTACGCCA;RSEQ=CAGCTCCAACTACCACAAGT;DUPRATE=0;SPLITREAD=0;SPANPAIR=0", "Otherinfo12": "GT:DP:VD:AD:AF:RD:ALD", "Otherinfo13": "0/1:1817:406:1407,406:0.2234:742,665:222,184" }, { "Validated": 1, "Chr": "chr12", "Start": 25398284, "End": 25398284, "Ref": "C", "Alt": "A", "AAChange.refGene": "KRAS:NM_004985:exon2:c.35G>T:p.G12V", "mutant_frequency": 0.2234, "total_reads": 1817, "mutant_reads": 406, "strand_bias": "222:184", "Otherinfo10": "PASS", "Func.refGene": "exonic", "Gene.refGene": "KRAS", "ExonicFunc.refGene": "nonsynonymous SNV", "avsnp150": "rs121913529", "cosmic91": "ID=COSV55497419;OCCURENCE=20(breast),1(female_genital_tract_(site_indeterminate)),7(liver),36(peritoneum),9(genital_tract),7(oesophagus),24(cervix),5668(large_intestine),1(central_nervous_system),189(biliary_tract),2(pleura),1(vulva),341(ovary),20(NS),45(stomach),90(haematopoietic_and_lymphoid_tissue),8(kidney),9(soft_tissue),32(urinary_tract),2142(pancreas),1(autonomic_ganglia),11(gastrointestinal_tract_(site_indeterminate)),30(skin),42(prostate),1579(lung),25(thyroid),5(upper_aerodigestive_tract),24(testis),4(thymus),1(eye),42(small_intestine),165(endometrium)", "CLNDN": "Acute_myeloid_leukemia|Cerebral_arteriovenous_malformation|Nevus_sebaceous|Juvenile_myelomonocytic_leukemia|Non-small_cell_lung_carcinoma|Neoplasm_of_the_thyroid_gland|Neoplasm_of_ovary|Neoplasm_of_the_large_intestine|Carcinoma_of_pancreas|not_provided", "CLNSIG": "Pathogenic", "ACMG_level": 1, "Deleterious": 2, "freq_high": 0, "OKBSIG": "Oncogenic", "AMP_evidence_level": "C", "AMP_mut_level": "II", "Indication": "实体瘤", "DrugCn": "贝美替尼", "Response_Type": "可能敏感", "Evidence_Source": "临床试验", "Efficacy_Evidence": "在一项I期临床试验中，纳入21位晚期实体瘤患者接受Binimetinib治疗，其中8例患者携带KRAS突变。在纳入分析的18例患者中，14例患者病情稳定，包含4例携带KRAS突变患者(PMID: 27071922)。", "Gene_function": "KRAS是小分子GTP酶RAS家族的成员，该家族催化GTP水解为GDP。在生理条件下，这些RAS蛋白在活性(GTP结合)和非活性(GDP结合)状态间循环，以激活受体酪氨酸激酶(RTK)下游的MAPK和PI3K致癌途径信号传导(PMID: 22189424)。RAS酶的功能受到鸟嘌呤核苷酸交换因子(GEF)如SOS的调节，这些因子可以使GDP与GTP交换，也可以通过GTP酶活化蛋白如NF1调节，提高RAS水解GTP的能力。一旦被激活，RAS可通过激活不同的细胞内信号传导途径(包括RAF/MEK/ERK和PI3K/AKT/mTOR途径)介导细胞增殖和其他细胞功能的调节。", "Drug_Category": "c", "Otherinfo11": "SAMPLE=2023WSSW000709-T;TYPE=SNV;DP=1817;VD=406;AF=0.2234;BIAS=2:2;REFBIAS=742:665;VARBIAS=222:184;PMEAN=39.5;PSTD=1;QUAL=34;QSTD=1;SBF=0.4986;ODDRATIO=1.08124472893195;MQ=60;SN=44.111;HIAF=0.2215;ADJAF=0.0083;SHIFT3=0;MSI=2;MSILEN=1;NM=1.2;HICNT=397;HICOV=1792;LSEQ=AGGCACTCTTGCCTACGCCA;RSEQ=CAGCTCCAACTACCACAAGT;DUPRATE=0;SPLITREAD=0;SPANPAIR=0", "Otherinfo12": "GT:DP:VD:AD:AF:RD:ALD", "Otherinfo13": "0/1:1817:406:1407,406:0.2234:742,665:222,184" }, { "Validated": 1, "Chr": "chr12", "Start": 25398284, "End": 25398284, "Ref": "C", "Alt": "A", "AAChange.refGene": "KRAS:NM_004985:exon2:c.35G>T:p.G12V", "mutant_frequency": 0.2234, "total_reads": 1817, "mutant_reads": 406, "strand_bias": "222:184", "Otherinfo10": "PASS", "Func.refGene": "exonic", "Gene.refGene": "KRAS", "ExonicFunc.refGene": "nonsynonymous SNV", "avsnp150": "rs121913529", "cosmic91": "ID=COSV55497419;OCCURENCE=20(breast),1(female_genital_tract_(site_indeterminate)),7(liver),36(peritoneum),9(genital_tract),7(oesophagus),24(cervix),5668(large_intestine),1(central_nervous_system),189(biliary_tract),2(pleura),1(vulva),341(ovary),20(NS),45(stomach),90(haematopoietic_and_lymphoid_tissue),8(kidney),9(soft_tissue),32(urinary_tract),2142(pancreas),1(autonomic_ganglia),11(gastrointestinal_tract_(site_indeterminate)),30(skin),42(prostate),1579(lung),25(thyroid),5(upper_aerodigestive_tract),24(testis),4(thymus),1(eye),42(small_intestine),165(endometrium)", "CLNDN": "Acute_myeloid_leukemia|Cerebral_arteriovenous_malformation|Nevus_sebaceous|Juvenile_myelomonocytic_leukemia|Non-small_cell_lung_carcinoma|Neoplasm_of_the_thyroid_gland|Neoplasm_of_ovary|Neoplasm_of_the_large_intestine|Carcinoma_of_pancreas|not_provided", "CLNSIG": "Pathogenic", "ACMG_level": 1, "Deleterious": 2, "freq_high": 0, "OKBSIG": "Oncogenic", "AMP_evidence_level": "D", "AMP_mut_level": "II", "Indication": "实体瘤", "DrugCn": "曲美替尼", "Response_Type": "可能敏感", "Evidence_Source": "临床前研究", "Efficacy_Evidence": "在一项临床前研究中，曲美替尼可抑制BRAF V600E和KRAS突变肿瘤细胞系的增殖，其IC50值低于PD0325901或selumetinib，虽然曲美替尼和PD0325901在体外对MEK1具有相似的效力。与PD0325901相比，在这些浓度下用曲美替尼或CH5126766处理48小时，可在KRAS突变细胞(H2030)和表达活性CRAF数量增加的A375细胞中更持久地抑制pERK活性(PMID: 24746704)。", "Gene_function": "KRAS是小分子GTP酶RAS家族的成员，该家族催化GTP水解为GDP。在生理条件下，这些RAS蛋白在活性(GTP结合)和非活性(GDP结合)状态间循环，以激活受体酪氨酸激酶(RTK)下游的MAPK和PI3K致癌途径信号传导(PMID: 22189424)。RAS酶的功能受到鸟嘌呤核苷酸交换因子(GEF)如SOS的调节，这些因子可以使GDP与GTP交换，也可以通过GTP酶活化蛋白如NF1调节，提高RAS水解GTP的能力。一旦被激活，RAS可通过激活不同的细胞内信号传导途径(包括RAF/MEK/ERK和PI3K/AKT/mTOR途径)介导细胞增殖和其他细胞功能的调节。", "Drug_Category": "c", "Otherinfo11": "SAMPLE=2023WSSW000709-T;TYPE=SNV;DP=1817;VD=406;AF=0.2234;BIAS=2:2;REFBIAS=742:665;VARBIAS=222:184;PMEAN=39.5;PSTD=1;QUAL=34;QSTD=1;SBF=0.4986;ODDRATIO=1.08124472893195;MQ=60;SN=44.111;HIAF=0.2215;ADJAF=0.0083;SHIFT3=0;MSI=2;MSILEN=1;NM=1.2;HICNT=397;HICOV=1792;LSEQ=AGGCACTCTTGCCTACGCCA;RSEQ=CAGCTCCAACTACCACAAGT;DUPRATE=0;SPLITREAD=0;SPANPAIR=0", "Otherinfo12": "GT:DP:VD:AD:AF:RD:ALD", "Otherinfo13": "0/1:1817:406:1407,406:0.2234:742,665:222,184" }, { "Validated": 1, "Chr": "chr12", "Start": 25398284, "End": 25398284, "Ref": "C", "Alt": "A", "AAChange.refGene": "KRAS:NM_004985:exon2:c.35G>T:p.G12V", "mutant_frequency": 0.2234, "total_reads": 1817, "mutant_reads": 406, "strand_bias": "222:184", "Otherinfo10": "PASS", "Func.refGene": "exonic", "Gene.refGene": "KRAS", "ExonicFunc.refGene": "nonsynonymous SNV", "avsnp150": "rs121913529", "cosmic91": "ID=COSV55497419;OCCURENCE=20(breast),1(female_genital_tract_(site_indeterminate)),7(liver),36(peritoneum),9(genital_tract),7(oesophagus),24(cervix),5668(large_intestine),1(central_nervous_system),189(biliary_tract),2(pleura),1(vulva),341(ovary),20(NS),45(stomach),90(haematopoietic_and_lymphoid_tissue),8(kidney),9(soft_tissue),32(urinary_tract),2142(pancreas),1(autonomic_ganglia),11(gastrointestinal_tract_(site_indeterminate)),30(skin),42(prostate),1579(lung),25(thyroid),5(upper_aerodigestive_tract),24(testis),4(thymus),1(eye),42(small_intestine),165(endometrium)", "CLNDN": "Acute_myeloid_leukemia|Cerebral_arteriovenous_malformation|Nevus_sebaceous|Juvenile_myelomonocytic_leukemia|Non-small_cell_lung_carcinoma|Neoplasm_of_the_thyroid_gland|Neoplasm_of_ovary|Neoplasm_of_the_large_intestine|Carcinoma_of_pancreas|not_provided", "CLNSIG": "Pathogenic", "ACMG_level": 1, "Deleterious": 2, "freq_high": 0, "OKBSIG": "Oncogenic", "AMP_evidence_level": "D", "AMP_mut_level": "II", "Indication": "实体瘤", "DrugCn": "RMC-6236", "Response_Type": "可能敏感", "Evidence_Source": "临床前研究", "Efficacy_Evidence": "在体外实验中，RMC-6236抑制了细胞生长，并诱导多种RAS癌细胞株凋亡，在临床前体内异种移植模型中，RMC-6236可抑制RAS通路的激活长达48小时。与健康组织相比RMC-6236对肿瘤组织的亲和力更高，在多种细胞系来源的异种移植模型（NSCLC、CRC和PDAC等）中RMC-6236对KRAS突变（特别是KRAS G12D, KRAS G12V和 KRAS G12R）均有明显也持久的肿瘤消退效果（Abstract: Koltun et al. Abstract# 3597, AACR 2022）。", "Gene_function": "KRAS是小分子GTP酶RAS家族的成员，该家族催化GTP水解为GDP。在生理条件下，这些RAS蛋白在活性(GTP结合)和非活性(GDP结合)状态间循环，以激活受体酪氨酸激酶(RTK)下游的MAPK和PI3K致癌途径信号传导(PMID: 22189424)。RAS酶的功能受到鸟嘌呤核苷酸交换因子(GEF)如SOS的调节，这些因子可以使GDP与GTP交换，也可以通过GTP酶活化蛋白如NF1调节，提高RAS水解GTP的能力。一旦被激活，RAS可通过激活不同的细胞内信号传导途径(包括RAF/MEK/ERK和PI3K/AKT/mTOR途径)介导细胞增殖和其他细胞功能的调节。", "Drug_Category": "c", "Otherinfo11": "SAMPLE=2023WSSW000709-T;TYPE=SNV;DP=1817;VD=406;AF=0.2234;BIAS=2:2;REFBIAS=742:665;VARBIAS=222:184;PMEAN=39.5;PSTD=1;QUAL=34;QSTD=1;SBF=0.4986;ODDRATIO=1.08124472893195;MQ=60;SN=44.111;HIAF=0.2215;ADJAF=0.0083;SHIFT3=0;MSI=2;MSILEN=1;NM=1.2;HICNT=397;HICOV=1792;LSEQ=AGGCACTCTTGCCTACGCCA;RSEQ=CAGCTCCAACTACCACAAGT;DUPRATE=0;SPLITREAD=0;SPANPAIR=0", "Otherinfo12": "GT:DP:VD:AD:AF:RD:ALD", "Otherinfo13": "0/1:1817:406:1407,406:0.2234:742,665:222,184" } ], "MET": [], "longindel": [], "MMR": [ { "gene": "MSH2", "transcript": "NM_000251", "c_change": "c.2425G>A", "p_change": "p.E809K", "freq": "51.85%", "muttype": "错义突变", "sig": "意义未明突变" } ], "sum": { "mmr": { "result_summary": "MSH2 p.E809K", "predict": "对免疫检查点抑制剂可能敏感", "mmr_num": 1 }, "chemo": { "drug_num": 22, "drug_category": { "常规": "卡铂,奥沙利铂,甲氨蝶呤,多西他赛,多柔比星", "推荐": "环磷酰胺,顺铂,卡培他滨,替加氟,替吉奥,吉西他滨,伊立替康,依托泊苷,紫杉醇,丝裂霉素,表柔比星,昂丹司琼,格拉司琼", "谨慎": "氟尿嘧啶,培美曲塞,长春新碱,长春瑞滨" } }, "hcs": { "num": 3 }, "hereditary": { "result": "TP53 p.V73Rfs*76", "disease": "Li-Fraumeni综合征", "risk": "结直肠癌,胰腺癌,甲状腺癌,胃癌,肾上腺皮质癌,乳腺癌,胶质母细胞瘤,星形细胞瘤,骨肉瘤,软组织肉瘤,急性淋巴细胞白血病,急性髓性白血病,骨髓增生异常综合征,淋巴瘤,头颈鳞癌,肾细胞癌,喉癌,肺癌,皮肤癌,卵巢癌,前列腺癌,睾丸癌,妊娠期绒毛膜癌" }, "signtb_num": 3, "signdrug_num": 8 }, "MSI": { "msi_count": 13, "msi_value": 0, "msi_result": "MSS", "msi_predict": "对免疫检查点抑制剂可能不敏感" }, "chemo": { "chemo_res": [ { "index": 1, "药物名称": "环磷酰胺", "疗效": 1, "毒副": 0, "推荐程度": "推荐", "疗效和毒副总结": "疗效较好" }, { "index": 2, "药物名称": "卡铂", "疗效": 2, "毒副": -1, "推荐程度": "常规", "疗效和毒副总结": "疗效较好,毒副较高" }, { "index": 3, "药物名称": "奥沙利铂", "疗效": 3, "毒副": -2, "推荐程度": "常规", "疗效和毒副总结": "疗效较好,毒副较高" }, { "index": 4, "药物名称": "顺铂", "疗效": 2, "毒副": 1, "推荐程度": "推荐", "疗效和毒副总结": "疗效较好,毒副较低" }, { "index": 5, "药物名称": "卡培他滨", "疗效": 0, "毒副": 9, "推荐程度": "推荐", "疗效和毒副总结": "毒副较低" }, { "index": 6, "药物名称": "替加氟", "疗效": 0, "毒副": 4, "推荐程度": "推荐", "疗效和毒副总结": "毒副较低" }, { "index": 7, "药物名称": "替吉奥", "疗效": 0, "毒副": 4, "推荐程度": "推荐", "疗效和毒副总结": "毒副较低" }, { "index": 8, "药物名称": "氟尿嘧啶", "疗效": 1, "毒副": -2, "推荐程度": "谨慎", "疗效和毒副总结": "疗效较好,毒副较高" }, { "index": 9, "药物名称": "吉西他滨", "疗效": 0, "毒副": 1, "推荐程度": "推荐", "疗效和毒副总结": "毒副较低" }, { "index": 10, "药物名称": "培美曲塞", "疗效": -2, "毒副": 0, "推荐程度": "谨慎", "疗效和毒副总结": "疗效较差" }, { "index": 11, "药物名称": "甲氨蝶呤", "疗效": 0, "毒副": 0, "推荐程度": "常规", "疗效和毒副总结": "毒副一般" }, { "index": 12, "药物名称": "伊立替康", "疗效": 0, "毒副": 2, "推荐程度": "推荐", "疗效和毒副总结": "毒副较低" }, { "index": 13, "药物名称": "依托泊苷", "疗效": 0, "毒副": 1, "推荐程度": "推荐", "疗效和毒副总结": "毒副较低" }, { "index": 14, "药物名称": "多西他赛", "疗效": -1, "毒副": 1, "推荐程度": "常规", "疗效和毒副总结": "疗效较差,毒副较低" }, { "index": 15, "药物名称": "紫杉醇", "疗效": 1, "毒副": 1, "推荐程度": "推荐", "疗效和毒副总结": "疗效较好,毒副较低" }, { "index": 16, "药物名称": "长春新碱", "疗效": -1, "毒副": 0, "推荐程度": "谨慎", "疗效和毒副总结": "疗效较差" }, { "index": 17, "药物名称": "长春瑞滨", "疗效": -1, "毒副": 0, "推荐程度": "谨慎", "疗效和毒副总结": "疗效较差" }, { "index": 18, "药物名称": "丝裂霉素", "疗效": 1, "毒副": 0, "推荐程度": "推荐", "疗效和毒副总结": "疗效较好" }, { "index": 19, "药物名称": "多柔比星", "疗效": 1, "毒副": -1, "推荐程度": "常规", "疗效和毒副总结": "疗效较好,毒副较高" }, { "index": 20, "药物名称": "表柔比星", "疗效": 2, "毒副": 0, "推荐程度": "推荐", "疗效和毒副总结": "疗效较好,毒副一般" }, { "index": 21, "药物名称": "昂丹司琼", "疗效": 2, "毒副": 0, "推荐程度": "推荐", "疗效和毒副总结": "疗效较好" }, { "index": 22, "药物名称": "格拉司琼", "疗效": 1, "毒副": 0, "推荐程度": "推荐", "疗效和毒副总结": "疗效较好" } ], "chemo_comb": { "结直肠癌": [ { "用药方案": "奥沙利铂+亚叶酸钙+氟尿嘧啶", "方案缩写": "FOLFOX", "source": "crc88gene", "临床提示": "慎用" }, { "用药方案": "伊立替康+亚叶酸钙+氟尿嘧啶", "方案缩写": "FOLFIRI", "source": "crc88gene", "临床提示": "慎用" }, { "用药方案": "奥沙利铂+卡培他滨", "方案缩写": "CAPEOX（又称Xelox）", "source": "crc88gene", "临床提示": "推荐" }, { "用药方案": "伊立替康+奥沙利铂+亚叶酸钙+氟尿嘧啶", "方案缩写": "FOLFOXIRI", "source": "crc88gene", "临床提示": "慎用" }, { "用药方案": "伊立替康+卡培他滨", "方案缩写": "CapIRI或XELIRI", "source": "crc88gene", "临床提示": "推荐" }, { "用药方案": "奥沙利铂+雷替曲塞", "方案缩写": "/", "source": "crc88gene", "临床提示": "可选" }, { "用药方案": "伊立替康+雷替曲塞", "方案缩写": "/", "source": "crc88gene", "临床提示": "推荐" } ] }, "chemo_info": { "丝裂霉素": [ { "检测基因": "NQO1", "检测位点": "rs1800566", "基因型": "GG", "证据等级": "3", "drugsort": 6, "用药提示": "疗效较好" } ], "伊立替康": [ { "检测基因": "UGT1A1", "检测位点": "rs3064744", "基因型": "TA[6]/TA[6]", "证据等级": "1A/1B", "drugsort": 5, "用药提示": "毒副较低" }, { "检测基因": "UGT1A1", "检测位点": "rs4148323", "基因型": "GG", "证据等级": "1A/1B", "drugsort": 5, "用药提示": "毒副较低" } ], "依托泊苷": [ { "检测基因": "DYNC2H1", "检测位点": "rs716274", "基因型": "AA", "证据等级": "3", "drugsort": 5, "用药提示": "毒副较低" } ], "卡培他滨": [ { "检测基因": "DPYD", "检测位点": "rs115232898", "基因型": "TT", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs1801266", "基因型": "GG", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs1801268", "基因型": "CC", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs55886062", "基因型": "AA", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs67376798", "基因型": "TT", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs72549303", "基因型": "GG", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs72549309", "基因型": "ATGA/ATGA", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs75017182", "基因型": "GG", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs3918290", "基因型": "CC", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" } ], "卡铂": [ { "检测基因": "ERCC1", "检测位点": "rs11615", "基因型": "AG", "证据等级": "3", "drugsort": 2, "用药提示": "毒副较高" }, { "检测基因": "XRCC1", "检测位点": "rs25487", "基因型": "CC", "证据等级": "2B", "drugsort": 2, "用药提示": "疗效较好" } ], "吉西他滨": [ { "检测基因": "CDA", "检测位点": "rs2072671", "基因型": "AA", "证据等级": "3", "drugsort": 4, "用药提示": "毒副较低" } ], "培美曲塞": [ { "检测基因": "MTHFR", "检测位点": "rs1801133", "基因型": "AG", "证据等级": "3", "drugsort": 4, "用药提示": "疗效较差" }, { "检测基因": "TYMS", "检测位点": "rs11280056", "基因型": "TTAAAG/del", "证据等级": "3", "drugsort": 4, "用药提示": "疗效较差" } ], "多柔比星": [ { "检测基因": "ABCB1", "检测位点": "rs2032582", "基因型": "AA", "证据等级": "3", "drugsort": 6, "用药提示": "疗效较好" }, { "检测基因": "HAS3", "检测位点": "rs2232228", "基因型": "AA", "证据等级": "3", "drugsort": 6, "用药提示": "毒副较高" } ], "多西他赛": [ { "检测基因": "CASP7", "检测位点": "rs2227310", "基因型": "CC", "证据等级": "3", "drugsort": 5, "用药提示": "疗效较差" }, { "检测基因": "CYP3A4", "检测位点": "rs2740574", "基因型": "TT", "证据等级": "3", "drugsort": 5, "用药提示": "毒副较低" } ], "奥沙利铂": [ { "检测基因": "XRCC1", "检测位点": "rs25487", "基因型": "CC", "证据等级": "2B", "drugsort": 2, "用药提示": "疗效较好" }, { "检测基因": "GSTP1", "检测位点": "rs1695", "基因型": "AA", "证据等级": "3", "drugsort": 2, "用药提示": "毒副较高" }, { "检测基因": "ERCC2", "检测位点": "rs13181", "基因型": "TT", "证据等级": "3", "drugsort": 2, "用药提示": "疗效较好" }, { "检测基因": "ERCC1", "检测位点": "rs11615", "基因型": "AG", "证据等级": "3", "drugsort": 2, "用药提示": "毒副较高" } ], "昂丹司琼": [ { "检测基因": "ABCB1", "检测位点": "rs2032582", "基因型": "AA", "证据等级": "3", "drugsort": 7, "用药提示": "疗效较好" }, { "检测基因": "ABCB1", "检测位点": "rs1045642", "基因型": "AA", "证据等级": "3", "drugsort": 7, "用药提示": "疗效较好" } ], "替加氟": [ { "检测基因": "DPYD", "检测位点": "rs67376798", "基因型": "TT", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs75017182", "基因型": "GG", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs3918290", "基因型": "CC", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs55886062", "基因型": "AA", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" } ], "替吉奥": [ { "检测基因": "DPYD", "检测位点": "rs3918290", "基因型": "CC", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs55886062", "基因型": "AA", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs67376798", "基因型": "TT", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs75017182", "基因型": "GG", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" } ], "格拉司琼": [ { "检测基因": "ABCB1", "检测位点": "rs1045642", "基因型": "AA", "证据等级": "3", "drugsort": 7, "用药提示": "疗效较好" } ], "氟尿嘧啶": [ { "检测基因": "DPYD", "检测位点": "rs72549303", "基因型": "GG", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "TYMS", "检测位点": "rs11280056", "基因型": "TTAAAG/del", "证据等级": "3", "drugsort": 3, "用药提示": "毒副较高" }, { "检测基因": "NQO1", "检测位点": "rs1800566", "基因型": "GG", "证据等级": "3", "drugsort": 3, "用药提示": "疗效较好" }, { "检测基因": "DPYD", "检测位点": "rs72549309", "基因型": "ATGA/ATGA", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs1801266", "基因型": "GG", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs1801268", "基因型": "CC", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs3918290", "基因型": "CC", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "GSTP1", "检测位点": "rs1695", "基因型": "AA", "证据等级": "3", "drugsort": 3, "用药提示": "毒副较高" }, { "检测基因": "DPYD", "检测位点": "rs75017182", "基因型": "GG", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs55886062", "基因型": "AA", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs67376798", "基因型": "TT", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" }, { "检测基因": "DPYD", "检测位点": "rs115232898", "基因型": "TT", "证据等级": "1A", "drugsort": 3, "用药提示": "毒副较低" } ], "环磷酰胺": [ { "检测基因": "SOD2", "检测位点": "rs4880", "基因型": "AG", "证据等级": "3", "drugsort": 1, "用药提示": "疗效居中" }, { "检测基因": "GSTP1", "检测位点": "rs1695", "基因型": "AA", "证据等级": "3", "drugsort": 1, "用药提示": "疗效较好" } ], "甲氨蝶呤": [ { "检测基因": "MTHFR", "检测位点": "rs1801133", "基因型": "AG", "证据等级": "2A", "drugsort": 4, "用药提示": "毒副居中" } ], "紫杉醇": [ { "检测基因": "CYP2C8", "检测位点": "rs11572080", "基因型": "CC", "证据等级": "3", "drugsort": 5, "用药提示": "毒副较低" }, { "检测基因": "ABCB1", "检测位点": "rs2032582", "基因型": "AA", "证据等级": "3", "drugsort": 5, "用药提示": "疗效较好" } ], "表柔比星": [ { "检测基因": "NQO1", "检测位点": "rs1800566", "基因型": "GG", "证据等级": "3", "drugsort": 6, "用药提示": "疗效较好" }, { "检测基因": "GSTP1", "检测位点": "rs1695", "基因型": "AA", "证据等级": "3", "drugsort": 6, "用药提示": "毒副较低,疗效较好" }, { "检测基因": "HAS3", "检测位点": "rs2232228", "基因型": "AA", "证据等级": "3", "drugsort": 6, "用药提示": "毒副较高" } ], "长春新碱": [ { "检测基因": "ABCB1", "检测位点": "rs1045642", "基因型": "AA", "证据等级": "3", "drugsort": 5, "用药提示": "疗效较差" } ], "长春瑞滨": [ { "检测基因": "CASP7", "检测位点": "rs2227310", "基因型": "CC", "证据等级": "3", "drugsort": 5, "用药提示": "疗效较差" } ], "顺铂": [ { "检测基因": "XRCC1", "检测位点": "rs25487", "基因型": "CC", "证据等级": "2B", "drugsort": 2, "用药提示": "疗效较好" }, { "检测基因": "XPC", "检测位点": "rs2228001", "基因型": "TT", "证据等级": "3", "drugsort": 2, "用药提示": "毒副较低" }, { "检测基因": "TPMT", "检测位点": "rs1142345", "基因型": "TT", "证据等级": "3", "drugsort": 2, "用药提示": "毒副较低" }, { "检测基因": "ERCC1", "检测位点": "rs11615", "基因型": "AG", "证据等级": "3", "drugsort": 2, "用药提示": "毒副较高" } ] } }, "HCS": [ { "Validated": 1, "Chr": "chr5", "Start": 112175447, "End": 112175447, "Ref": "A", "Alt": "T", "Func.refGene": "exonic", "Gene.refGene": "APC", "GeneDetail.refGene": ".", "ExonicFunc.refGene": "stopgain", "AAChange.refGene": "APC:NM_000038:exon16:c.4156A>T:p.R1386X", "avsnp150": ".", "cosmic91": "ID=COSV57330977;OCCURENCE=6(large_intestine)", "CLNALLELEID": ".", "CLNDN": ".", "CLNDISDB": ".", "CLNREVSTAT": ".", "CLNSIG": ".", "1000g2015aug_all": ".", "1000g2015aug_eas": ".", "esp6500siv2_all": ".", "ExAC_nontcga_ALL": ".", "ACMG_level": 3 }, { "Validated": 1, "Chr": "chr12", "Start": 25398284, "End": 25398284, "Ref": "C", "Alt": "A", "Func.refGene": "exonic", "Gene.refGene": "KRAS", "GeneDetail.refGene": ".", "ExonicFunc.refGene": "nonsynonymous SNV", "AAChange.refGene": "KRAS:NM_004985:exon2:c.35G>T:p.G12V", "avsnp150": "rs121913529", "cosmic91": "ID=COSV55497419;OCCURENCE=20(breast),1(female_genital_tract_(site_indeterminate)),7(liver),36(peritoneum),9(genital_tract),7(oesophagus),24(cervix),5668(large_intestine),1(central_nervous_system),189(biliary_tract),2(pleura),1(vulva),341(ovary),20(NS),45(stomach),90(haematopoietic_and_lymphoid_tissue),8(kidney),9(soft_tissue),32(urinary_tract),2142(pancreas),1(autonomic_ganglia),11(gastrointestinal_tract_(site_indeterminate)),30(skin),42(prostate),1579(lung),25(thyroid),5(upper_aerodigestive_tract),24(testis),4(thymus),1(eye),42(small_intestine),165(endometrium)", "CLNALLELEID": "27622", "CLNDN": "Acute_myeloid_leukemia|Cerebral_arteriovenous_malformation|Nevus_sebaceous|Juvenile_myelomonocytic_leukemia|Non-small_cell_lung_carcinoma|Neoplasm_of_the_thyroid_gland|Neoplasm_of_ovary|Neoplasm_of_the_large_intestine|Carcinoma_of_pancreas|not_provided", "CLNDISDB": "Human_Phenotype_Ontology:HP:0001914,Human_Phenotype_Ontology:HP:0004808,Human_Phenotype_Ontology:HP:0004843,Human_Phenotype_Ontology:HP:0005516,Human_Phenotype_Ontology:HP:0006724,Human_Phenotype_Ontology:HP:0006728,MONDO:MONDO:0018874,MeSH:D015470,MedGen:C0023467,OMIM:601626,Orphanet:ORPHA519,SNOMED_CT:17788007|Human_Phenotype_Ontology:HP:0002408,MONDO:MONDO:0007154,MedGen:C0917804,OMIM:108010,Orphanet:ORPHA46724,SNOMED_CT:234142008|Human_Phenotype_Ontology:HP:0010815,MedGen:C3854181|Human_Phenotype_Ontology:HP:0012209,MONDO:MONDO:0011908,MedGen:C0349639,OMIM:607785,Orphanet:ORPHA86834|Human_Phenotype_Ontology:HP:0030358,MONDO:MONDO:0005233,MeSH:D002289,MedGen:C0007131,SNOMED_CT:254637007|Human_Phenotype_Ontology:HP:0100031,MONDO:MONDO:0015074,MeSH:D013964,MedGen:C0040136,Orphanet:ORPHA100087|Human_Phenotype_Ontology:HP:0100615,MONDO:MONDO:0021068,MeSH:D010051,MedGen:C0919267,OMIM:167000,SNOMED_CT:123843001|Human_Phenotype_Ontology:HP:0100834,MeSH:D015179,MedGen:C0009404,SNOMED_CT:126837005|MONDO:MONDO:0005192,MeSH:C562463,MedGen:C0235974,OMIM:260350,Orphanet:ORPHA217074,SNOMED_CT:372142002|MedGen:CN517202", "CLNREVSTAT": "criteria_provided,_multiple_submitters,_no_conflicts", "CLNSIG": "Pathogenic", "1000g2015aug_all": ".", "1000g2015aug_eas": ".", "esp6500siv2_all": ".", "ExAC_nontcga_ALL": ".", "ACMG_level": 1 }, { "Validated": 1, "Chr": "chr17", "Start": 7579470, "End": 7579470, "Ref": "-", "Alt": "G", "Func.refGene": "exonic", "Gene.refGene": "TP53", "GeneDetail.refGene": ".", "ExonicFunc.refGene": "frameshift insertion", "AAChange.refGene": "TP53:NM_000546:exon4:c.216dupC:p.V73Rfs*76", "avsnp150": "rs730882018", "cosmic91": "ID=COSV52710145;OCCURENCE=2(salivary_gland),3(breast),1(oesophagus),8(large_intestine),1(biliary_tract),2(stomach),1(haematopoietic_and_lymphoid_tissue),1(soft_tissue),3(pancreas),5(skin),4(prostate),3(lung),4(upper_aerodigestive_tract)", "CLNALLELEID": "181025", "CLNDN": "Multiple_myeloma|Hereditary_cancer-predisposing_syndrome|Li-Fraumeni_syndrome|Li-Fraumeni-like_syndrome|Breast_and/or_ovarian_cancer", "CLNDISDB": "Human_Phenotype_Ontology:HP:0006775,MONDO:MONDO:0009693,MeSH:D009101,MedGen:C0026764,OMIM:254500,Orphanet:ORPHA29073,SNOMED_CT:109989006,SNOMED_CT:55921005|MONDO:MONDO:0015356,MedGen:C0027672,Orphanet:ORPHA140162,SNOMED_CT:699346009|MONDO:MONDO:0018875,MedGen:C0085390,OMIM:PS151623,Orphanet:ORPHA524,SNOMED_CT:428850001|MedGen:C2675080|MedGen:CN221562", "CLNREVSTAT": "criteria_provided,_multiple_submitters,_no_conflicts", "CLNSIG": "Pathogenic", "1000g2015aug_all": ".", "1000g2015aug_eas": ".", "esp6500siv2_all": ".", "ExAC_nontcga_ALL": ".", "ACMG_level": 1 } ], "hereditary": [ { "基因": "TP53", "遗传性肿瘤综合征": "Li-Fraumeni综合征", "遗传方式": "AD", "杂合/纯合": "杂合", "检测结果": "p.V73Rfs*76" } ], "qc": { "raw_reads": 9598256, "raw_bases": 1439738400, "clean_reads": 9488546, "clean_bases": 1406177980, "clean_reads_rate(%)": 98.86, "Q20(%)": 97.89, "q30": 94.32, "mapped_reads": 9471537, "mapped_rate(%)": 99.82, "dup_reads": 2485892, "dup_rate(%)": 26.25, "probe_bed_size": 493464, "target_reads": 5448673, "capture_rate(reads)": 57.53, "mean_depth_raw": 1298.63, "depth": 937.62, "coverage(>0x)": 47.05, "coverage(>10x)": 41.56, "coverage": 35.53, "coverage(>=80%)": 0 }, "indication": [ { "基因": "BRAF", "检测内容": "突变", "检测情况": "未检出变异", "肿瘤类型": "结直肠癌/实体瘤" }, { "基因": "ERBB2", "检测内容": "扩增", "检测情况": "未检出变异", "肿瘤类型": "结直肠癌" }, { "基因": "KRAS", "检测内容": "突变", "检测情况": "未检出变异", "肿瘤类型": "结直肠癌" }, { "基因": "NRAS", "检测内容": "突变", "检测情况": "未检出变异", "肿瘤类型": "结直肠癌" }, { "基因": "NTRK1", "检测内容": "突变/融合", "检测情况": "未检出变异", "肿瘤类型": "实体瘤" }, { "基因": "NTRK2", "检测内容": "融合", "检测情况": "未检出变异", "肿瘤类型": "实体瘤" }, { "基因": "NTRK3", "检测内容": "突变/融合", "检测情况": "未检出变异", "肿瘤类型": "实体瘤" }, { "基因": "RET", "检测内容": "融合", "检测情况": "未检出变异", "肿瘤类型": "实体瘤" } ], "drugs": { "drugs_detail": { "西妥昔单抗": "ERBITUX是一种表皮生长因子受体(EGFR)拮抗剂，其适应症包括：1.联合放疗用于治疗局部或区域晚期头颈鳞癌。2.联合铂类和氟尿嘧啶用于治疗头颈部复发性局部疾病或转移性头颈鳞癌。3.铂类治疗后进展的复发性或转移性头颈鳞癌。4.联合FOLFIRI用于K-Ras野生型、EGFR表达阳性的转移性结直肠癌的一线治疗。5.联合伊立替康用于治疗对基于伊立替康化疗耐药的K-Ras野生型、EGFR表达阳性的转移性结直肠癌患者。6.单药用于治疗对奥沙利铂和伊立替康为基础的化疗失败或对伊立替康不耐受的K-Ras野生型、EGFR表达阳性的转移性结直肠癌患者。7.联合康奈非尼用于先前治疗后携带BRAF V600E突变的转移性结直肠癌(CRC)成人患者。\\\\表皮生长因子受体（EGFR，HER1，c-ErbB-1）是一种跨膜糖蛋白，是I型受体酪氨酸激酶亚家族（包括EGFR，HER2，HER3和HER4）的成员。EGFR在包括皮肤和毛囊在内的许多正常上皮组织中组成性表达。EGFR的表达在许多人类肿瘤（包括头颈部、结肠和直肠癌）中也能检测到。西妥昔单抗(Cetuximab)可以特异性地与正常细胞和肿瘤细胞表面的EGFR结合,竞争性抑制EGFR与表皮生长因子（EGF）或其他配体（如转化生长因子-α）的结合。体外试验和体内动物研究表明，西妥昔单抗(Cetuximab)与EGFR的结合可阻断受体相关激酶的磷酸化和激活，从而抑制细胞生长，诱导细胞凋亡，降低基质金属蛋白酶和血管内皮生长因子的生成。EGFR信号转导可导致野生型Ras蛋白的激活，但在有Ras体细胞激活突变的细胞中，Ras突变蛋白处于持续激活状态，且独立于EGFR的调控。在体外，西妥昔单抗(Cetuximab)可介导针对某些类型的人类肿瘤的抗体依赖性细胞介导的细胞毒作用（ADCC）。体外试验和体内动物研究表明，西妥昔单抗(Cetuximab)可抑制表达EGFR肿瘤细胞的生长和存活。在缺乏EGFR表达的人肿瘤异种移植模型中未观察到西妥昔单抗(Cetuximab)的抗肿瘤作用。在小鼠人源肿瘤异种移植模型中，放疗或伊立替康(Irinotecan)加用西妥昔单抗(Cetuximab)后，抗肿瘤效果比单纯放疗或化疗更好。", "曲妥珠单抗": "Herceptin是一种HER2/neu受体拮抗剂，其适应症为：1.HER2过表达的乳腺癌。2.HER2过表达的转移性胃或胃食管交界处腺癌。\\\\HER2（或c-erbB2）原癌基因编码一个185 kDa的跨膜受体蛋白，该蛋白在结构上与表皮生长因子受体有关。曲妥珠单抗/赫赛汀（Trastuzumab/Herceptin）在体外及动物实验中均显示出可抑制HER2过表达肿瘤细胞的增殖。曲妥珠单抗/赫赛汀（Trastuzumab/Herceptin）是抗体依赖性细胞毒性（ADCC）的介体。在体外研究中，与未过表达HER2的癌细胞相比，曲妥珠单抗/赫赛汀（Trastuzumab/Herceptin）介导的ADCC优先作用于过表达HER2的癌细胞。", "妥卡替尼": "TUKYSA是一种激酶抑制剂，其适应证为：1.联合曲妥珠单抗和卡培他滨治疗既往转移治疗中接受过一种或多种抗HER2治疗的晚期不可切除性或转移性HER2阳性乳腺癌成人患者，包括发生脑转移的患者。2.联合曲妥珠单抗治疗患者之前在氟嘧啶、奥沙利铂和伊立替康化疗治疗后进展的RAS野生型，HER2阳性不可切除或转移性结直肠癌患者，。\\\\Tucatinib是HER2的酪氨酸激酶抑制剂。 在体外试验中，Tucatinib能够抑制HER2和HER3磷酸化，从而抑制下游MAPK和AKT信号通路和细胞增殖，并且在表达HER2的肿瘤细胞中显示出抗肿瘤活性。在体内研究中，Tucatinib可以抑制表达HER2肿瘤的生长。与单独使用这两种药物相比，Tucatinib和曲妥珠单抗（Trastuzumab)联合在体外试验和体内研究中均表现出增强的抗肿瘤活性。", "帕尼单抗": "Vectibix是一种表皮生长因子受体(EGFR)拮抗剂，其适应症为：1.联合FOLFOX用于RAS野生型(KRAS和NRAS均为野生型)转移性结直肠癌(mCRC)的一线治疗。2.单药用于治疗既往接受含氟嘧啶类、奥沙利铂和伊立替康化疗后疾病进展的RAS野生型mCRC。\\\\跨膜糖蛋白EGFR是I型受体酪氨酸激酶（包括EGFR，HER2，HER3和HER4）亚家族的成员。EGFR在包括皮肤和毛囊在内的正常上皮组织中组成性表达。某些人类癌症（包括结肠癌和直肠癌）中EGFR过表达。EGFR与其正常配体（例如EGF、转化生长因子-α）的相互作用导致一系列胞内蛋白的磷酸化和激活，继而调节与细胞生长、存活、运动性以及增殖相关基因的转录。KRAS（Kirsten大鼠肉瘤病毒癌基因同源物）和NRAS（神经母细胞瘤RAS病毒癌基因同源物）是RAS癌基因家族中高度相关的成员。通过EGFR的信号转导可导致野生型KRAS和NRAS蛋白激活。然而，在具有RAS体细胞激活突变的细胞中，RAS突变蛋白处于持续激活状态，不依赖EGFR的调控。帕尼单抗（Panitumumab）可以与正常细胞和肿瘤细胞上的EGFR特异性结合，并竞争性抑制EGFR配体的结合。非临床研究表明，帕尼单抗（Panitumumab）与EGFR结合可阻止配体诱导的受体自磷酸化和受体相关激酶的激活，从而抑制细胞生长、诱导细胞凋亡、减少促炎细胞因子和血管生长因子的产生以及EGFR的内在化。体外试验和体内动物研究表明，帕尼单抗（Panitumumab）可以抑制某些表达EGFR人类肿瘤细胞系的生长和存活。", "帕妥珠单抗": "PERJETA是一种HER2/neu受体拮抗剂，其适应症为：1.联合曲妥珠单抗和多西紫杉醇用于治疗既往未接受过抗HER2治疗或转移性疾病化疗的HER2阳性转移性乳腺癌(MBC)。2.联合曲妥珠单抗和化疗用于：(1)HER2阳性的局部晚期、炎性或早期乳腺癌(直径大于2cm或淋巴结阳性)的新辅助治疗，作为早期乳腺癌整体治疗方案的一部分。(2)具有复发高风险的HER2阳性早期乳腺癌的辅助治疗。\\\\帕妥珠单抗（Pertuzumab）靶向细胞外人表皮生长因子受体2蛋白（HER2）的二聚化结构域（子结构域Ⅱ），从而阻断HER2与其它HER家族成员（包括EGFR、HER3和HER4）的配体依赖性异源二聚化作用。结果，帕妥珠单抗（Pertuzumab）通过两条主要信号途径（有丝分裂原激活蛋白[MAP]激酶和磷酸肌醇3激酶[PI3K]）抑制配体启动的细胞内信号传导。这些信号通路的抑制分别导致细胞生长停滞和凋亡。此外，帕妥珠单抗（Pertuzumab）介导抗体依赖性细胞介导的细胞毒性作用（ADCC）。尽管单独使用帕妥珠单抗（Pertuzumab）能抑制人肿瘤细胞的增殖，但在过表达HER2的异种移植模型中，帕妥珠单抗（Pertuzumab）和曲妥珠单抗（Trastuzumab）联合可以增强抗肿瘤活性。", "拉帕替尼": "TYKERB是一种激酶抑制剂，其适应症为：1.联合卡培他滨用于治疗过表达人表皮生长因子受体2(HER2)并且既往接受过蒽环类、紫杉类和曲妥珠单抗等治疗的晚期或转移性乳腺癌。2.联合来曲唑用于治疗过表达HER2受体适用激素治疗的绝经后妇女激素受体阳性转移性乳腺癌。\\\\拉帕替尼（Lapatinib）是一种4-苯胺喹唑啉类抑制剂，可抑制人表皮生长因子受体（EGFR [ErbB1]）和人表皮生长因子受体2（HER2 [ErbB2]）的胞内酪氨酸激酶结构域活性（预估Kiapp值分别为3 nM和13 nM），消除半衰期大于或等于300分钟。拉帕替尼（Lapatinib）可在体外和各种动物模型中抑制ErbB驱动的肿瘤细胞生长。在一项体外研究的4种受试肿瘤细胞系中，拉帕替尼（Lapatinib）和 5-FU（卡培他滨的活性代谢物）联合用药显示出相加作用。在对曲妥珠单抗（Trastuzumab）耐受的细胞系中拉帕替尼（Lapatinib）的生长抑制作用已得到评估。拉帕替尼（Lapatinib）对于可在含曲妥珠单抗（Trastuzumab）培养基中长期生长的乳腺癌细胞系也保持显著活性。这些体外研究表明，这两种药物之间没有交叉耐药性。共表达HER2的激素受体阳性乳腺癌细胞（如雌激素受体[ER]和/或孕激素受体[PgR]）易对内分泌治疗产生耐受。同样，激素受体阳性乳腺癌细胞缺乏EGFR或HER2时会上调这些受体蛋白表达，使肿瘤对内分泌治疗耐受。", "考比替尼": "COTELLIC是一种激酶抑制剂，其适应症为联合维莫非尼用于治疗携带BRAF V600E或V600K突变的不可切除性或转移性黑色素瘤。\\\\考比替尼(Cobimetinib)是一种靶向有丝分裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶1（MEK1）和MEK2的可逆抑制剂。MEK蛋白是细胞外信号调节激酶(ERK)通路的上游调控蛋白，该通路可促进细胞增殖。BRAF V600E和K突变导致包括MEK1和MEK2在内的BRAF途径的组成性激活。在移植表达BRAF V600E肿瘤细胞系的小鼠中，考比替尼(Cobimetinib)抑制了肿瘤细胞的生长。考比替尼(Cobimetinib)和维罗非尼(Vemurafenib)靶向RAS/RAF/MEK/ERK通路的两种不同激酶。与单独使用这两种药物相比，考比替尼(Cobimetinib)和维罗非尼(Vemurafenib)联合用药在体外可增加细胞凋亡，在植入表达BRAF V600E突变的肿瘤细胞系的小鼠中可抑制肿瘤生长。此外,在小鼠肿瘤细胞移植模型中,考比替尼(Cobimetinib)还可以阻止维罗非尼(Vemurafenib)介导的野生型BRAF肿瘤细胞系的生长。", "贝美替尼": "MEKTOVI是一种激酶抑制剂，联合康奈非尼用于治疗BRAF V600E或V600K突变的不可切除性或转移性黑色素瘤。\\\\贝美替尼(Binimetinib)是一种有丝分裂原激活的细胞外信号调节激酶1（MEK1）和MEK2活性的可逆抑制剂。MEK蛋白是细胞外信号相关激酶（ERK）途径的上游调控蛋白。在体外，贝美替尼(Binimetinib)在非细胞试验中能抑制细胞外信号相关激酶(ERK)的磷酸化，并抑制了BRAF突变型人黑素瘤细胞系的活力和MEK依赖性磷酸化。在BRAF突变的小鼠异种移植瘤模型中，贝美替尼(Binimetinib)也能抑制体内ERK磷酸化和肿瘤生长。贝美替尼(Binimetinib)和康奈非尼(Encorafenib)靶向RAS/RAF/MEK/ERK通路的两种不同激酶。与单独使用任何一种药物相比，康奈非尼(Encorafenib)和贝美替尼(Binimetinib)联合用药在体外对BRAF突变阳性细胞系产生更强的抗增殖活性，且在BRAF V600E突变型人类黑色素瘤小鼠异种移植研究中，对肿瘤生长抑制显示出更强的抗肿瘤活性。此外，与单独使用两种药物相比，联合使用贝美替尼(Binimetinib)和康奈非尼(Encorafenib)延缓了BRAF V600E突变型人黑色素瘤小鼠异种移植瘤模型耐药性的出现。", "曲美替尼": "MEKINIST是一种激酶抑制剂，其适应症为：1.单药用于治疗携带BRAF V600E或V600K突变的不可切除性或转移性黑色素瘤。2.联合达拉菲尼用于：(1)携带BRAF V600E或V600K突变的不可切除性或转移性黑色素瘤。(2)携带BRAF V600E或V600K突变且完全切除后累及淋巴结的黑色素瘤患者的辅助治疗。(3)携带BRAF V600E突变的转移性非小细胞肺癌(NSCLC)。(4)没有令人满意的局部区域治疗选择的BRAF V600E突变的局部晚期或转移性间变性甲状腺癌(ATC)。(5)携带BRAF V600E突变的不可切除或转移性实体瘤成人和6岁及以上的儿童患者的治疗，且这些患者在之前的治疗后进展，没有满意的替代治疗方案。（6）需要接受系统治疗并携带BRAF V600E突变的低级别胶质瘤( LGG )患者（1岁及以上）。\\\\曲美替尼（Trametinib）是有丝分裂原激活的细胞外信号调节激酶1（MEK1）和MEK2激活以及MEK1和MEK2激酶活性的可逆抑制剂。MEK蛋白是细胞外信号相关激酶（ERK）途径的上游调控因子，可促进细胞增殖。BRAF V600E突变导致包括MEK1和MEK2在内的BRAF途径的组成性激活。曲美替尼（Trametinib）在体外和体内抑制各种BRAF V600突变阳性肿瘤细胞的生长。曲美替尼（Trametinib）和达拉非尼（Dabrafenib）靶向RAS/RAF/MEK/ERK通路中的两种不同激酶。与单独使用这两种药物相比，曲美替尼（Trametinib）和达拉非尼（Dabrafenib）联合用药可加强对BRAF V600突变阳性肿瘤细胞系生长的抑制作用，并延长对BRAF V600突变阳性肿瘤异种移植物肿瘤生长的抑制作用。", "阿培利司": "PIQRAY是一种激酶抑制剂，适用于联合氟维司群用于治疗既往接受内分泌治疗后疾病进展、携带PIK3CA突变、激素受体(HR)阳性、人表皮生长因子受体2 (HER2)阴性的绝经后妇女和男性晚期或转移性乳腺癌。\\\\阿培利司（Alpelisib）是PI3Kα的抑制剂，主要具有针对PI3Kα的抑制活性。在体外和体内模型中，PIK3CA基因的获得性突变将导致PI3Kα和Akt信号通路的激活，从而使细胞性状发生转化以及促使肿瘤的产生。在乳腺癌细胞系中，阿培利司（Alpelisib）抑制PI3K下游靶标（包括Akt）的磷酸化，并在具有PIK3CA突变的细胞系中显示出活性。在体内，阿培利司（Alpelisib）在移植瘤模型（包括乳腺癌模型）中抑制PI3K/Akt信号通路并降低肿瘤生长。通过阿培利司（Alpelisib）治疗抑制PI3K已显示出可诱导乳腺癌细胞中雌激素受体（ER）转录的增加。在ER阳性、PIK3CA突变的乳腺癌细胞系的移植瘤模型中，阿培利司（Alpelisib）和氟维司琼（Fulvestrant）联合治疗显示出较单一治疗更强的抗肿瘤活性。", "RLY-2608": "RLY-2608是一种新型变构、泛突变、选择性PI3Kα抑制剂,一项临床I期研究正在评估RLY-2608作为单药在PI3KCA突变的晚期实体瘤患者( pts )中的临床活性，以及联合氟维司群在PIK3CA突变、HR +、HER2 -转移性乳腺癌( MBC )患者中的临床活性。", "培唑帕尼": "VOTRIENT是一种激酶抑制剂，适用于晚期肾细胞癌(RCC)和既往接受过化疗的晚期软组织肉瘤(STS)成人患者。\\\\培唑帕尼（Pazopanib）是血管内皮生长因子受体（VEGFR）-1/2/3，血小板衍生生长因子受体（PDGFR）-α/β，成纤维细胞生长因子受体（FGFR）-1/3，细胞因子受体（Kit），白介素2受体诱导的T细胞激酶（Itk），淋巴细胞特异性蛋白酪氨酸激酶（Lck）和跨膜糖蛋白受体酪氨酸激酶（c-Fms）的多靶点酪氨酸激酶抑制剂。 在体外，培唑帕尼（Pazopanib）抑制配体诱导的VEGFR-2、Kit和PDGFR-β受体自身磷酸化。 在体内，培唑帕尼（Pazopanib）抑制小鼠肺中VEGF诱导的VEGFR-2磷酸化、小鼠模型的血管生成以及小鼠中某些人源肿瘤异种移植物的生长。", "伏立诺他": "ZOLINZA是一种组蛋白去乙酰化酶(HDAC)抑制剂，用于治疗在两种全身治疗期间或之后出现进展，持续或复发疾病的的皮肤T细胞淋巴瘤(CTCL)患者的皮肤表现。\\\\伏立诺他(Vorinostat)可在纳摩尔级浓度下抑制组蛋白脱乙酰基酶HDAC1、HDAC2和HDAC3（I类）和HDAC6（II类）的酶活性（IC50 < 86 nM）。这些酶催化去除组蛋白赖氨酸残基上的乙酰基基团。在某些肿瘤细胞中，HDACs过表达，或异常募集到致癌的转录因子上，导致核小体核心组蛋白乙酰化不足。伏立诺他(Vorinostat)通过抑制组蛋白脱乙酰基酶来导致乙酰化组蛋白的累积，并诱导某些转化细胞的细胞周期停滞和/或凋亡。伏立诺他(Vorinostat)抗肿瘤作用的机制尚未完全阐明。", "贝伐珠单抗": "Avastin是一种血管内皮生长因子抑制剂，其适应症为：1.与基于氟尿嘧啶的静脉化疗联合用于转移性结直肠癌的一线或二线治疗。2.与基于氟嘧啶-伊立替康或氟嘧啶-奥沙利铂的化疗联合用于含Avastin一线方案治疗后疾病进展的转移性结直肠癌的二线治疗。3.与卡铂、紫杉醇联合用于不可切除的、局部晚期、复发性或转移性非鳞状非小细胞肺癌的一线治疗。4.成人复发性胶质母细胞瘤。5.联合干扰素α用于治疗转移性肾细胞癌。6.与紫杉醇、顺铂或紫杉醇、拓扑替康联合，用于治疗持续性、复发性或转移性宫颈癌。7.上皮性卵巢癌、输卵管癌或原发性腹膜癌：(1)与卡铂和紫杉醇联合，然后使用Avastin单药，用于治疗首次手术切除后的III期或IV期疾病。(2)与紫杉醇、聚乙二醇脂质体多柔比星或拓扑替康联合，用于治疗既往接受不超过2个化疗方案的铂耐复发性疾病。(3)与卡铂、紫杉醇或卡铂、吉西他滨联合，然后使用Avastin单药，用于治疗铂敏感复发性疾病。8.与Atezolizumab联合用于治疗既往未接受过全身治疗的不可切除或转移性肝细胞癌(HCC)患者。\\\\Bevacizumab结合VEGF并阻止VEGF与其内皮细胞表面的受体(Flt-1和KDR)相互作用。在体外血管生成模型中，VEGF与其受体的相互作用导致内皮细胞增殖和新血管形成。在裸鼠结肠癌异种移植模型中给予贝伐单抗，导致微血管生长减少和转移疾病进展的抑制。", "司美替尼": "KOSELUGO是一种激酶抑制剂，适用于2岁及以上患有1型神经纤维瘤(NF1)、有症状的、不能手术的丛状神经纤维瘤(PN)的儿童患者。\\\\Selumetinib是丝裂原活化蛋白激酶激酶1和2（MEK1/2）的抑制剂。MEK1/2蛋白是细胞外信号相关激酶（ERK）途径的上游调节因子。MEK和ERK都是RAS调节的RAF-MEK-ERK通路的关键组成部分，该通路通常在不同类型的癌症中被激活。在产生与人类NF1基因型和表型相似的神经纤维瘤的转基因NF1小鼠模型中，口服塞洛替尼抑制ERK磷酸化，并减少神经纤维瘤的数量、体积和增殖。" }, "drugs_type": { "可能敏感": [ "Ipatasertib", "RMC-6236", "考比替尼", "曲美替尼", "贝美替尼", "RLY-2608", "阿培利司", "贝伐珠单抗", "培唑帕尼", "伏立诺他" ], "耐药": [ "曲妥珠单抗", "帕妥珠单抗", "EGFR-TKI", "帕尼单抗", "妥卡替尼", "拉帕替尼", "trastuzumab deruxtecan", "西妥昔单抗" ] } } }