From 1b7cd252fc7ef2fe74972f6cd6b70afbaa627bca Mon Sep 17 00:00:00 2001 From: chaopower Date: Thu, 10 Aug 2023 09:35:50 +0800 Subject: [PATCH] =?UTF-8?q?=E8=B0=83=E6=95=B4=E6=96=87=E4=BB=B6?= MIME-Version: 1.0 Content-Type: text/plain; charset=UTF-8 Content-Transfer-Encoding: 8bit --- .gitignore | 4 +- main.py | 3 +- result/2023WSSW000709-T.docx | Bin 657163 -> 657178 bytes t.json | 1608 ---------------------------------- template/~$report.docx | Bin 162 -> 0 bytes 5 files changed, 3 insertions(+), 1612 deletions(-) delete mode 100644 t.json delete mode 100644 template/~$report.docx diff --git a/.gitignore b/.gitignore index 1834aff..2bce4c4 100644 --- a/.gitignore +++ b/.gitignore @@ -212,10 +212,10 @@ log/* example/* !example/readme.md -/xlsx/ +xlsx/*xlsx !xlsx/readme.md -/result/ +result/*docx !result/readme.md /.report/ \ No newline at end of file diff --git a/main.py b/main.py index 5c4d4df..6419c48 100644 --- a/main.py +++ b/main.py @@ -1,6 +1,5 @@ import json import os -import socket import sys from docxtpl import DocxTemplate @@ -21,4 +20,4 @@ def main(path): if __name__ == '__main__': - main(sys.argv[1]) \ No newline at end of file + main(sys.argv[1]) diff --git a/result/2023WSSW000709-T.docx b/result/2023WSSW000709-T.docx index aa64dabd5d2cf06126aca221584d4158767f893d..bf6671b3f1ef3c704055780e1564a51ccd5f8dbd 100644 GIT binary patch delta 173967 zcmZsBV{|6L^KNY0wr$(CZF{3Pwr$%sH`*i{Yh&AXa`XG+oO{o?AEvvydU~e1PtWx8 zR8@2wRaP7ooRTak7#a`|5EPKDN+a9`Fo>;6^BFKcFtn`-h^FMdu9HeL66mlI0KOyE zu?kwH_wIdUy)1R>t-asyqk*x|>D&8|Al~EpyZZUO_Udzc__!Y7mg~dqv6=UC44w9g zMZb7Zk(~iL5*tzKVr*t~jpde0g+pqU$lUd8qKqN{Vwv}mBv%jkLe+6eD~thOWMc#q z03O7!^LV5T<#|TAI&mNwcmraN3|crGHr?2QV_#B!Nur2x@zf}B*8zy zU7X`8czjW=W6)}k)CW!phZu~R!*Es3;UR>u-wrs*k2bx#6!vOhs&@kbIw8pCE@xVB8 zF2-}ttMxv9-+B19vkX7nKsV5Hpm14(^k^`MVDP2FFUxc8ZE#C~&G~BlrlP~=?b%kJ z^8W2#$Vz;%_SL3v`y~nqG=nq~|v(t8N%Z|2)`0_zl&UMkLDTDGze3ql3z zx$E7VKt9c?yVtG{kb<2e5c+$}ZKF`PK*zT;^0NL?JVth%E~ZpKnH@rrK%?<1ZEdC!6yfYbIZO2b^I 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"source": "蜡卷 血液", - "makeTime": "2023-03-07 00:00:00", - "receiveTime": "2023-03-09", - "reportTime": "2023-08-01", - "remark": "先转百道包埋2.26组织转百道3.9百道回蜡卷", - "idCard": "", - "lockStatus": 0, - "waringTime": "2023-03-15 09:26:30", - "division": "/", - "zlType": "/", - "familySn": "/", - "estimateEndTime": "2023-03-16 09:26:30", - "doctorUserId": 0, - "areaAgentId": 1253, - "agentId": 2008, - "unitAgentId": 2007, - "labId": 0, - "orderType": "/", - "receiveStatus": 1, - "sampleInfoId": 94313702, - "gender": "女", - "age": 79, - "contactAddr": "/", - "familyRel": "/", - "birthday": "/", - "treatmentNo": "/", - "treatHistory": "/", - "sickFamilyHistory": "/", - "treatResult": "结肠癌" - }, - "snvindel": [ - { - "gene": "APC", - "transcript": "NM_000038", - "exon": "exon16", - "nacid": "c.4385_4386del", - "aacid": "p.S1465Wfs*3", - "mutant_frequency": "38.21%", - "AMP_mut_level": "III", - "muttype": "移码突变", - "Gene_function": ".", - "drug_category": {}, - "drug_content": [], - "alter": "APC:NM_000038:exon16:c.4385_4386del:p.S1465Wfs*3" - }, - { - "gene": "BRAF", - "transcript": "NM_004333", - "exon": "exon15", - "nacid": "c.1799T>A", - "aacid": "p.V600E", - "mutant_frequency": "67.37%", - "AMP_mut_level": "I", - "muttype": "错义突变", - "Gene_function": "BRAF是MAP激酶级联信号通路中一种重要的丝氨酸/苏氨酸蛋白激酶。当生长因子与受体结合时,受体的酪氨酸激酶结构域激活并通过RAS激酶向下游发出信号。RAF蛋白是活化RAS蛋白的直接效应因子(PMID: 8503013; PMID: 8327501)。RAF二聚体(BRAF,ARAF,CRAF)通过磷酸化和激活MEK进一步传递该级联信号(PMID: 24957944)。激活的MEK-ERK信号可以促进细胞增殖、存活、迁移和分化。BRAF的存在对正常发育至关重要;然而,不受抑制的BRAF信号可以促进肿瘤发生。", - "drug_category": { - "a": "康奈非尼 + 西妥昔单抗 【A 级】\n曲美替尼 【A 级】\n达拉非尼 + 曲美替尼 【A 级】\n达拉非尼 【A 级】\n康奈非尼 + 帕尼单抗 【A 级】", - "c": "维莫非尼 【C 级】\n维莫非尼 + 考比替尼 【C 级】\n康奈非尼 + 贝美替尼 【C 级】\n维莫非尼 + 考比替尼 + 阿替利珠单抗 【C 级】\n维莫非尼 【C 级】\n维莫非尼 + 考比替尼 【C 级】\n维莫非尼 + 考比替尼 【C 级】\n维莫非尼 + 考比替尼 【C 级】\n司美替尼 【C 级】\n康奈非尼 【C 级】\n维莫非尼,达拉非尼 【C 级】\n维莫非尼 + 考比替尼 【C 级】\n康奈非尼 + 贝美替尼 【C 级】\n达拉非尼,曲美替尼 【C 级】\n维莫非尼,考比替尼 【C 级】\n康奈非尼,贝美替尼 【C 级】\n贝美替尼 + 康奈非尼 + 西妥昔单抗 【B 级】", - "d": "达拉非尼 【A 级】\n曲美替尼 【C 级】\nEGFR-TKI 【C 级】" - }, - "drug_content": [ - { - "index": 0, - "DrugCn": "康奈非尼 + 西妥昔单抗", - "Response_Type": "敏感", - "Indication": "结直肠癌", - "Evidence_Source": "FDA", - "Efficacy_Evidence": "FDA批准康奈非尼联合西妥昔单抗用于BRAF V600E突变的转移性结直肠癌(CRC)成人患者的二线治疗(FDA-approval: 04/2020)。" - }, - { - "index": 1, - "DrugCn": "曲美替尼", - "Response_Type": "敏感", - "Indication": "实体瘤", - "Evidence_Source": "FDA", - "Efficacy_Evidence": "FDA推荐Trametinib用于治疗携带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。" - }, - { - "index": 2, - "DrugCn": "达拉非尼 + 曲美替尼", - "Response_Type": "敏感", - "Indication": "实体瘤", - "Evidence_Source": "FDA", - "Efficacy_Evidence": "FDA推荐Trametinib联合Dabrafenib用于治疗携带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,且Trametinib不适合治疗结直肠癌患者((FDA-approval:06/2022)。" - }, - { - "index": 3, - "DrugCn": "达拉非尼", - "Response_Type": "耐药", - "Indication": "结直肠癌", - "Evidence_Source": "FDA", - "Efficacy_Evidence": "因为BRAF耐药性,FDA不推荐Dabrafenib用于结直肠癌患者的治疗,因为BRAF抑制内在耐药。TAFINLAR不适用于野生型BRAF实体瘤的治疗(FDA-approval: 06/2022)。" - }, - { - "index": 4, - "DrugCn": "达拉非尼", - "Response_Type": "敏感", - "Indication": "实体瘤", - "Evidence_Source": "FDA", - "Efficacy_Evidence": "TAFINLAR适用于携带BRAF V600突变的不可切除或转移性6岁及以上的成人和儿童实体瘤患者,且这些患者在之前的治疗后进展且没有合适的替代治疗方案(FDA-approval: 06/2022)。" - }, - { - "index": 5, - "DrugCn": "康奈非尼 + 帕尼单抗", - "Response_Type": "敏感", - "Indication": "结直肠癌", - "Evidence_Source": "NCCN", - "Efficacy_Evidence": "NCCN指南建议使用Encorafenib + Panitumumab治疗携带BRAF基因V600E突变的晚期或转移性结直肠癌患者(NCCN: Colon Cancer-Version 2.2021)。" - }, - { - "index": 6, - "DrugCn": "维莫非尼", - "Response_Type": "敏感", - "Indication": "黑色素瘤", - "Evidence_Source": "FDA", - "Efficacy_Evidence": "Vemurafenib是一种激酶抑制剂,FDA批准用于治疗携带BRAF V600E突变的不可切除性或转移性黑色素瘤(FDA-approval: 05/2020)。" - }, - { - "index": 7, - "DrugCn": "维莫非尼 + 考比替尼", - "Response_Type": "敏感", - "Indication": "黑色素瘤", - "Evidence_Source": "FDA", - "Efficacy_Evidence": "FDA批准Cobimetinib联合Vemurafenib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(FDA-approval: 05/2020)。" - }, - { - "index": 8, - "DrugCn": "康奈非尼 + 贝美替尼", - "Response_Type": "敏感", - "Indication": "黑色素瘤", - "Evidence_Source": "FDA", - "Efficacy_Evidence": "FDA批准Encorafenib联合Binimetinib用于治疗BRAF V600E或V600K突变的不可切除性或转移性黑色素瘤(FDA-approval: 01/2019)。" - }, - { - "index": 9, - "DrugCn": "维莫非尼 + 考比替尼 + 阿替利珠单抗", - "Response_Type": "敏感", - "Indication": "黑色素瘤", - "Evidence_Source": "FDA", - "Efficacy_Evidence": "Vemurafenib是一种激酶抑制剂,FDA批准联合Cobimetinib和Vemurafenib用于治疗BRAF V600突变阳性的不可切除性或转移性黑色素瘤(FDA-approval: 05/2020)。在一项三期临床试验中,Cobimetinib、Vemurafenib和Atezolizumab联合治疗与对照组(Cobimetinib+Vemurafenib+Atezolizumab安慰剂)相比可显著增加BRAF(V600)突变的晚期黑色素瘤患者的无进展生存期(PMID:32534646)。" - }, - { - "index": 10, - "DrugCn": "维莫非尼", - "Response_Type": "可能敏感", - "Indication": "非小细胞肺癌", - "Evidence_Source": "NCCN", - "Efficacy_Evidence": "NCCN指南建议使用Vemurafenib治疗携带BRAF V600E突变的非小细胞肺癌(NSCLC)(NCCN: Non-Small Cell Lung Cancer-Version 4.2021)。" - }, - { - "index": 11, - "DrugCn": "维莫非尼 + 考比替尼", - "Response_Type": "敏感", - "Indication": "神经胶质瘤", - "Evidence_Source": "NCCN", - "Efficacy_Evidence": "NCCN指南推荐Vemurafenib+Cobimetinib用于治疗携带BRAF V600E突变的神经胶质瘤患者(NCCN: Central Nervous System Cancers-Version 2.2021)。" - }, - { - "index": 12, - "DrugCn": "维莫非尼 + 考比替尼", - "Response_Type": "敏感", - "Indication": "纤维性星型细胞瘤", - "Evidence_Source": "NCCN", - "Efficacy_Evidence": "NCCN指南指出Vemurafenib+Cobimetinib可用于治疗携带BRAF V600E突变的毛状星细胞瘤患者(NCCN: Central Nervous System Cancers-Version 2.2021)。" - }, - { - "index": 13, - "DrugCn": "维莫非尼 + 考比替尼", - "Response_Type": "敏感", - "Indication": "多型性星型细胞瘤", - "Evidence_Source": "NCCN", - "Efficacy_Evidence": "NCCN指南指出Vemurafenib+Cobimetinib可用于治疗携带BRAF V600E突变的多形性黄色星形细胞瘤患者(NCCN: Central Nervous System Cancers-Version 2.2021)。" - }, - { - "index": 14, - "DrugCn": "司美替尼", - "Response_Type": "敏感", - "Indication": "纤维性星型细胞瘤", - "Evidence_Source": "NCCN", - "Efficacy_Evidence": "NCCN指南推荐Selumetinib用于治疗BRAF融合或BRAF V600E突变阳性、复发性或进展性毛状星细胞瘤(NCCN: Central Nervous System Cancers-Version 1.2021; PMID: 31151904)。" - }, - { - "index": 15, - "DrugCn": "康奈非尼", - "Response_Type": "可能敏感", - "Indication": "黑色素瘤", - "Evidence_Source": "NCCN", - "Efficacy_Evidence": "NCCN指南指出Encorafenib单药治疗对携带BRAF V600E突变的皮肤黑色素瘤患者敏感(NCCN: Melanoma Cutaneous-Version 2.2021)。" - }, - { - "index": 16, - "DrugCn": "维莫非尼,达拉非尼", - "Response_Type": "可能敏感", - "Indication": "甲状腺癌", - "Evidence_Source": "NCCN", - "Efficacy_Evidence": "NCCN指南指出Vemurafenib, Dabrafenib可用于治疗携带BRAF V600E突变的甲状腺癌患者的进展性或症状性疾病(NCCN: Thyroid Carcinoma-Version 3.2021)。" - }, - { - "index": 17, - "DrugCn": "曲美替尼", - "Response_Type": "可能耐药", - "Indication": "葡萄膜黑色素瘤", - "Evidence_Source": "NCCN", - "Efficacy_Evidence": "NCCN指南不推荐Trametinib用于治疗BRAF或KIT突变的葡萄膜黑色素瘤患者(NCCN: Melanoma Uveal-Version 2.2021)。" - }, - { - "index": 18, - "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和BRAF基因突变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": 19, - "DrugCn": "维莫非尼 + 考比替尼", - "Response_Type": "敏感", - "Indication": "黑色素瘤", - "Evidence_Source": "NCCN", - "Efficacy_Evidence": "NCCN指南建议Vemurafenib + Cobimetinib治疗携带BRAF基因V600突变的转移性或不可切除的皮肤黑色素瘤(NCCN: Melanoma Cutaneous-Version 2.2021)。" - }, - { - "index": 20, - "DrugCn": "康奈非尼 + 贝美替尼", - "Response_Type": "敏感", - "Indication": "黑色素瘤", - "Evidence_Source": "NCCN", - "Efficacy_Evidence": "NCCN指南建议Encorafenib + Binimetinib治疗携带BRAF基因V600突变的转移性或不可切除的皮肤黑色素瘤(NCCN: Melanoma Cutaneous-Version 2.2021)。" - }, - { - "index": 21, - "DrugCn": "达拉非尼,曲美替尼", - "Response_Type": "敏感", - "Indication": "皮肤黑色素瘤", - "Evidence_Source": "NCCN", - "Efficacy_Evidence": "NCCN指南推荐trametinib或Dabrafenib用于治疗携带 BRAF V600热点突变的皮肤黑色素瘤患者(NCCN: Hepatobiliary Cancers-Version 3.2022)。" - }, - { - "index": 22, - "DrugCn": "维莫非尼,考比替尼", - "Response_Type": "敏感", - "Indication": "皮肤黑色素瘤", - "Evidence_Source": "NCCN", - "Efficacy_Evidence": "NCCN指南推荐Vemurafenib或cobimetinib用于治疗携带 BRAF V600热点突变的皮肤黑色素瘤患者(NCCN: Hepatobiliary Cancers-Version 3.2022)。" - }, - { - "index": 23, - "DrugCn": "康奈非尼,贝美替尼", - "Response_Type": "敏感", - "Indication": "皮肤黑色素瘤", - "Evidence_Source": "NCCN", - "Efficacy_Evidence": "NCCN指南推荐Encorafenib,binimetinib用于治疗携带 BRAF V600热点突变的皮肤黑色素瘤患者(NCCN: Hepatobiliary Cancers-Version 3.2022)。" - }, - { - "index": 24, - "DrugCn": "贝美替尼 + 康奈非尼 + 西妥昔单抗", - "Response_Type": "敏感", - "Indication": "结直肠癌", - "Evidence_Source": "临床III期", - "Efficacy_Evidence": "在一项III期临床试验中,29位携带BRAF V600E突变的转移性结直肠癌患者使用Binimetinib + Encorafenib + Cetuximab联合治疗后,其总体缓解率为48% (95% CI, 29.4%-67.5%), 中位PFS为8个月(95% CI, 5.6-9.3个月), 中位总生存期为15.3个月,该试验的中位随访期为18.2个月(PMID: 30892987)。" - } - ], - "alter": "BRAF:NM_004333:exon15:c.1799T>A:p.V600E" - }, - { - "gene": "FBXW7", - "transcript": "NM_033632", - "exon": "exon9", - "nacid": "c.1313C>T", - "aacid": "p.S438F", - "mutant_frequency": "42.79%", - "AMP_mut_level": "III", - "muttype": "错义突变", - "Gene_function": ".", - "drug_category": {}, - "drug_content": [], - "alter": "FBXW7:NM_033632:exon9:c.1313C>T:p.S438F" - }, - { - "gene": "IDH1", - "transcript": "NM_005896", - "exon": "exon6", - "nacid": "c.623A>G", - "aacid": "p.Y208C", - "mutant_frequency": "45.45%", - "AMP_mut_level": "III", - "muttype": "错义突变", - "Gene_function": ".", - "drug_category": {}, - "drug_content": [], - "alter": "IDH1:NM_005896:exon6:c.623A>G:p.Y208C" - }, - { - "gene": "KRAS", - "transcript": "NM_004985", - "exon": "exon2", - "nacid": "c.38G>A", - "aacid": "p.G13D", - "mutant_frequency": "39.35%", - "AMP_mut_level": "I", - "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": "Irinotecan + 司美替尼 【B 级】\n曲美替尼 【C 级】\n考比替尼 + Ipatasertib 【C 级】\n贝美替尼 【C 级】\n曲美替尼 【D 级】", - "d": "西妥昔单抗 【A 级】\n曲妥珠单抗 + 妥卡替尼 【A 级】\n帕尼单抗 【A 级】\n曲妥珠单抗 + 帕妥珠单抗,曲妥珠单抗 + 拉帕替尼,trastuzumab deruxtecan 【A 级】\nEGFR-TKI 【C 级】" - }, - "drug_content": [ - { - "index": 25, - "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": 26, - "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": 27, - "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": 28, - "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": 29, - "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": 30, - "DrugCn": "Irinotecan + 司美替尼", - "Response_Type": "可能敏感", - "Indication": "结直肠癌", - "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)。" - }, - { - "index": 31, - "DrugCn": "曲美替尼", - "Response_Type": "可能敏感", - "Indication": "结直肠癌", - "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)。" - }, - { - "index": 32, - "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": 33, - "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": 34, - "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)。" - } - ], - "alter": "KRAS:NM_004985:exon2:c.38G>A:p.G13D" - }, - { - "gene": "RAD54L", - "transcript": "NM_001142548", - "exon": "exon11", - "nacid": "c.1052A>G", - "aacid": "p.H351R", - "mutant_frequency": "47.02%", - "AMP_mut_level": "III", - "muttype": "错义突变", - "Gene_function": ".", - "drug_category": {}, - "drug_content": [], - "alter": "RAD54L:NM_001142548:exon11:c.1052A>G:p.H351R" - }, - { - "gene": "SMO", - "transcript": "NM_005631", - "exon": "exon2", - "nacid": "c.371C>T", - "aacid": "p.P124L", - "mutant_frequency": "3.99%", - "AMP_mut_level": "III", - "muttype": "错义突变", - "Gene_function": ".", - "drug_category": {}, - "drug_content": [], - "alter": "SMO:NM_005631:exon2:c.371C>T:p.P124L" - }, - { - "gene": "TP53", - "transcript": "NM_000546", - "exon": "exon6", - "nacid": "c.637C>T", - "aacid": "p.R213X", - "mutant_frequency": "67.37%", - "AMP_mut_level": "II", - "muttype": "提前终止", - "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": 35, - "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": 36, - "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:exon6:c.637C>T:p.R213X" - } - ], - "fusion": [], - "cnv": [ - { - "index": 0, - "Gene_Symbol": "CCND3", - "Copy_number": 7.5, - "AMP_mut_level": "II", - "Gene_function": "CCND3 (细胞周期蛋白D3)蛋白通过激活细胞周期蛋白依赖性激酶4 (CDK4)和CDK6,将细胞外生长因子信号与细胞周期的启动相连接(PMID: 8114739)。CDK4和CDK6与细胞周期蛋白D3形成复合物后磷酸化视网膜母细胞瘤蛋白(RB)并使其失活,进而诱导由E2F转录因子家族调控的基因程序性表达,这在细胞周期从G1到S期的过渡中很重要(PMID: 12432268)。细胞周期蛋白D3对于细胞周期的启动不是必需的(PMID: 15315760),并且在人类癌症中很少有扩增或过表达(PMID: 21734724)。然而,细胞周期蛋白D3-CDK6复合物可能通过抑制糖酵解途径中的关键酶在肿瘤细胞的代谢和存活中发挥促进作用(PMID: 28607489)。", - "muttype": "扩增", - "drug_category": { - "c": "阿贝西利 【D 级】" - }, - "drug_content": [ - { - "index": 0, - "DrugCn": "阿贝西利", - "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,具有某些D-细胞周期蛋白激活特征的癌细胞 (DCAF癌症) 对CDK4/6抑制剂abemaciclib特别敏感,CCND2扩增是DCAF的一种(PMID: 29232554)。" - } - ], - "alter": "CCND3 扩增" - } - ], - "hotspot": [], - "MET": [], - "longindel": [], - "MMR": [], - "sum": { - "mmr": { - "result_summary": "未检测到相关基因突变", - "predict": "对免疫检查点抑制剂可能不敏感", - "mmr_num": 0 - }, - "chemo": { - "drug_num": 22, - "drug_category": { - "常规": "卡铂,多西他赛,丝裂霉素,多柔比星", - "推荐": "环磷酰胺,卡培他滨,替加氟,替吉奥,培美曲塞,甲氨蝶呤,伊立替康,紫杉醇,表柔比星", - "谨慎": "奥沙利铂,顺铂,氟尿嘧啶,吉西他滨,依托泊苷,长春新碱,长春瑞滨,昂丹司琼,格拉司琼" - } - }, - "hcs": { - "num": 6 - }, - "hereditary": { - "result": "APC p.S1465Wfs*3|TP53 p.R213X", - "disease": "家族性腺瘤样息肉病|Li-Fraumeni综合征", - "risk": "结直肠癌,小肠腺癌,胰腺癌,甲状腺癌,髓母细胞瘤,肝母细胞瘤,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": 4, - "signdrug_num": 19 - }, - "MSI": { - "msi_count": 18, - "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": 2, - "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": "疗效较差,毒副较低" - }, - { - "index": 3, - "药物名称": "奥沙利铂", - "疗效": -1, - "毒副": 0, - "推荐程度": "谨慎", - "疗效和毒副总结": "疗效较差,毒副一般" - }, - { - "index": 4, - "药物名称": "顺铂", - "疗效": -2, - "毒副": -1, - "推荐程度": "谨慎", - "疗效和毒副总结": "疗效较差,毒副较高" - }, - { - "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": 0, - "毒副": -2, - "推荐程度": "谨慎", - "疗效和毒副总结": "疗效一般,毒副较高" - }, - { - "index": 9, - "药物名称": "吉西他滨", - "疗效": 0, - "毒副": -1, - "推荐程度": "谨慎", - "疗效和毒副总结": "毒副较高" - }, - { - "index": 10, - "药物名称": "培美曲塞", - "疗效": 2, - "毒副": 0, - "推荐程度": "推荐", - "疗效和毒副总结": "疗效较好" - }, - { - "index": 11, - "药物名称": "甲氨蝶呤", - "疗效": 0, - "毒副": 2, - "推荐程度": "推荐", - "疗效和毒副总结": "毒副较低" - }, - { - "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": "谨慎", - "疗效和毒副总结": "毒副较高" - }, - { - "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": 0, - "毒副": 1, - "推荐程度": "推荐", - "疗效和毒副总结": "疗效一般,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": 0, - "毒副": 0, - "推荐程度": "常规", - "疗效和毒副总结": "疗效一般" - }, - { - "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": 1, - "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": "谨慎", - "疗效和毒副总结": "疗效较差" - }, - { - "index": 22, - "药物名称": "格拉司琼", - "疗效": -1, - "毒副": 0, - "推荐程度": "谨慎", - "疗效和毒副总结": "疗效较差" - } - ], - "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": "慎用" - }, - { - "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": "慎用" - }, - { - "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": "AG", - "证据等级": "3", - "drugsort": 6, - "用药提示": "疗效居中" - } - ], - "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": "AG", - "证据等级": "3", - "drugsort": 5, - "用药提示": "毒副较高" - } - ], - "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": "GG", - "证据等级": "3", - "drugsort": 2, - "用药提示": "毒副较低" - }, - { - "检测基因": "XRCC1", - "检测位点": "rs25487", - "基因型": "TT", - "证据等级": "2B", - "drugsort": 2, - "用药提示": "疗效较差" - } - ], - "吉西他滨": [ - { - "检测基因": "CDA", - "检测位点": "rs2072671", - "基因型": "CC", - "证据等级": "3", - "drugsort": 4, - "用药提示": "毒副较高" - } - ], - "培美曲塞": [ - { - "检测基因": "MTHFR", - "检测位点": "rs1801133", - "基因型": "GG", - "证据等级": "3", - "drugsort": 4, - "用药提示": "疗效较好" - }, - { - "检测基因": "TYMS", - "检测位点": "rs11280056", - "基因型": "del/del", - "证据等级": "3", - "drugsort": 4, - "用药提示": "疗效较好" - } - ], - "多柔比星": [ - { - "检测基因": "ABCB1", - "检测位点": "rs2032582", - "基因型": "AC", - "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": "AG", - "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": "TT", - "证据等级": "2B", - "drugsort": 2, - "用药提示": "疗效较差" - }, - { - "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": "GG", - "证据等级": "3", - "drugsort": 2, - "用药提示": "毒副较低" - } - ], 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- "CLNREVSTAT": "criteria_provided,_conflicting_interpretations", - "CLNSIG": "Conflicting_interpretations_of_pathogenicity", - "1000g2015aug_all": ".", - "1000g2015aug_eas": ".", - "esp6500siv2_all": ".", - "ExAC_nontcga_ALL": ".", - "ACMG_level": 1 - }, - { - "Validated": 1, - "Chr": "chr17", - "Start": 7578212, - "End": 7578212, - "Ref": "G", - "Alt": "A", - "Func.refGene": "exonic", - "Gene.refGene": "TP53", - "GeneDetail.refGene": ".", - "ExonicFunc.refGene": "stopgain", - "AAChange.refGene": "TP53:NM_000546:exon6:c.637C>T:p.R213X", - "avsnp150": "rs397516436", - "cosmic91": "ID=COSV52665560;OCCURENCE=4(salivary_gland),79(breast),2(penis),1(peritoneum),9(liver),59(oesophagus),1(adrenal_gland),1(cervix),142(large_intestine),20(central_nervous_system),10(biliary_tract),1(pleura),15(ovary),2(bone),9(NS),19(haematopoietic_and_lymphoid_tissue),38(stomach),12(urinary_tract),9(soft_tissue),6(kidney),28(pancreas),50(skin),10(prostate),30(lung),8(thyroid),42(upper_aerodigestive_tract),2(small_intestine),28(endometrium)", - "CLNALLELEID": "52759", - "CLNDN": "Li-Fraumeni_syndrome_1|Neoplasm_of_ovary|Malignant_Colorectal_Neoplasm|Squamous_cell_carcinoma_of_the_head_and_neck|Hereditary_cancer-predisposing_syndrome|Familial_cancer_of_breast|Li-Fraumeni_syndrome|not_specified|not_provided", - "CLNDISDB": "Gene:553989,MONDO:MONDO:0007903,MedGen:C1835398,OMIM:151623|Human_Phenotype_Ontology:HP:0100615,MONDO:MONDO:0021068,MeSH:D010051,MedGen:C0919267,OMIM:167000,SNOMED_CT:123843001|MONDO:MONDO:0005575,MedGen:C0346629,OMIM:114500|MONDO:MONDO:0010150,MeSH:D000077195,MedGen:C1168401,OMIM:275355,SNOMED_CT:716659002|MONDO:MONDO:0015356,MedGen:C0027672,Orphanet:ORPHA140162,SNOMED_CT:699346009|MONDO:MONDO:0016419,MedGen:C0346153,OMIM:114480,Orphanet:ORPHA227535,SNOMED_CT:254843006|MONDO:MONDO:0018875,MedGen:C0085390,OMIM:PS151623,Orphanet:ORPHA524,SNOMED_CT:428850001|MedGen:CN169374|MedGen:CN517202", - "CLNREVSTAT": "criteria_provided,_multiple_submitters,_no_conflicts", - "CLNSIG": "Pathogenic", - "1000g2015aug_all": ".", - "1000g2015aug_eas": ".", - "esp6500siv2_all": ".", - "ExAC_nontcga_ALL": ".", - "ACMG_level": 1 - } - ], - "hereditary": [ - { - "基因": "APC", - "遗传性肿瘤综合征": "家族性腺瘤样息肉病", - "遗传方式": "AD", - "杂合/纯合": "杂合", - "检测结果": "p.S1465Wfs*3" - }, - { - "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.R213X" - } - ], - "qc": { - "raw_reads": 25806702, - "raw_bases": 3871005300, - "clean_reads": 25435480, - "clean_bases": 3775883686, - "clean_reads_rate(%)": 98.56, - "Q20(%)": 97.48, - "q30": 93.25, - "mapped_reads": 25427831, - "mapped_rate(%)": 99.97, - "dup_reads": 7120246, - "dup_rate(%)": 28, - "probe_bed_size": 493464, - "target_reads": 21612699, - "capture_rate(reads)": 85, - "mean_depth_raw": 4958.03, - "depth": 3467.06, - "coverage(>0x)": 100, - "coverage(>10x)": 100, - "coverage": 99.34, - "coverage(>=80%)": 2211 - }, - "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": { - "康奈非尼": "BRAFTOVI是一种激酶抑制剂,其适应症为:1.联合贝美替尼用于治疗BRAF V600E或V600K突变的不可切除性或转移性黑色素瘤。2.联合西妥昔单抗用于BRAF V600E突变的转移性结直肠癌(CRC)成人患者的二线治疗。\\\\康奈非尼(Enasidenib)是异柠檬酸脱氢酶2(IDH2)酶的小分子抑制剂。 在体外康奈非尼(Enasidenib)靶向结合IDH2突变R140Q、R172S和R172K的能力比野生型酶高约40倍。 康奈非尼(Enasidenib)对IDH2突变酶的抑制导致2-羟基戊二酸(2-HG)水平降低,可在体外试验和IDH2突变AML的小鼠异种移植模型中诱导髓样分化。 在携带IDH2突变AML患者的血液样本中,康奈非尼(Enasidenib)可降低2-HG水平,减少原始细胞(blast)计数,并增加成熟髓样细胞的百分比。", - "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。", - "达拉非尼": "TAFINLAR是一种激酶抑制剂,其适应症为:1.单药用于治疗BRAF V600E突变的不可切除性或转移性黑色素瘤。2.联合曲美替尼用于:(1)BRAF V600E或V600K突变的不可切除性或转移性黑色素瘤。(2)BRAF V600E或V600K突变、手术切除后累及淋巴结的黑色素瘤的辅助治疗。(3)BRAF V600E突变的转移性非小细胞肺癌(NSCLC)。(4)BRAF V600E突变且没有令人满意的局部治疗选择的局部晚期或转移性间变性甲状腺癌(ATC)。(5)适用于携带BRAF V600突变的不可切除或转移性6岁及以上的成人和儿童实体瘤患者,且这些患者在之前的治疗后进展且没有合适的替代治疗方案。(6)携带BRAF V600E突变需要全身治疗的儿童(1岁及以上)胶质瘤患者 备注:BRAF抑制具有耐药性,因此TAFINLAR不用于结直肠癌患者的治疗,TAFINLAR也不适用于野生型BRAF实体瘤的治疗。使用限制:TAFINLAR不用于结直肠癌患者的治疗,因为已知的BRAF抑制内在耐药(1.7,12.1)。TAFINLAR不适用于野生型BRAF实体瘤的治疗\\\\达拉菲尼(Dabrafenib)是一种靶向抑制剂,对一些BRAF突变如BRAF V600E、V600K和V600D的体外IC50值分别为0.65、0.5和1.84nM。达拉菲尼(Dabrafenib)也可以抑制野生型BRAF和CRAF激酶活性,IC50值分别为3.2和5.0nM,在更高浓度下还可以抑制其他激酶,如SIK1、NEK11和LIMK1。BRAF基因的一些突变,例如BRAF V600E突变,可以导致BRAF激酶的组成性激活,从而刺激肿瘤细胞的生长。无论是在体外还是在体内研究中,达拉菲尼(Dabrafenib)都可以抑制各种BRAF V600突变阳性肿瘤细胞的生长。达拉菲尼(Dabrafenib)和曲美替尼(Trametinib)靶向RAS/RAF/MEK/ERK通路的两种不同激酶。与单独使用两种药物相比,达拉菲尼(Dabrafenib)和曲美替尼(Trametinib)联合使用可增强对BRAF V600突变阳性肿瘤细胞系的生长抑制效果,并延长对BRAF V600突变阳性肿瘤异种移植模型的生长抑制作用。", - "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。", - "维莫非尼": "ZELBORAF是一种激酶抑制剂,其适应症为:1.携带BRAF V600E突变的不可切除性或转移性黑色素瘤。2.携带BRAF V600突变的Erdheim-Chester病。\\\\维罗非尼(Vemurafenib)是一种低分子量、口服可吸收的BRAF丝氨酸-苏氨酸激酶突变体(包括BRAF V600E)抑制剂。维罗非尼(Vemurafenib)还可以在体外以相似的浓度抑制其他激酶活性,如CRAF、ARAF、野生型BRAF、SRMS、ACK1、MAP4K5和FGR。包括V600E在内的BRAF基因突变会导致BRAF蛋白被组成性激活,从而在缺乏生长因子(通常在细胞增殖中必需)的情况下引起细胞增殖。维罗非尼(Vemurafenib)在BRAF V600E突变黑素瘤的细胞和动物模型中具有抗肿瘤作用。", - "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。", - "阿替利珠单抗": "TECENTRIQ是一种程序性死亡配体1(PD-L1)阻断抗体,其适应症包括:1.下列局部晚期或转移性尿路上皮癌成人患者:(1)不适用顺铂化疗、且肿瘤表达PD-L1(PD-L1染色的肿瘤浸润免疫细胞[IC]覆盖≥5%肿瘤面积)。(2)不论PD-L1的状态如何,均不适用任何含铂化疗。2.转移性非小细胞肺癌(NSCLC):(1) 用于(肿瘤细胞中PD-L1表达≥1%)II - IIIA期非小细胞肺癌切除和铂基化疗后的辅助治疗。(2)用于肿瘤高表达PD-L1(PD-L1染色≥50%肿瘤细胞[TC≥50%]或PD-L1染色的肿瘤浸润免疫细胞[IC]覆盖≥10%的肿瘤面积[IC≥10%])、无EGFR或ALK基因组肿瘤异常的转移性NSCLC成人患者的一线治疗。(3)联合贝伐珠单抗、紫杉醇和卡铂用于无EGFR或ALK基因组肿瘤异常的转移性非鳞状NSCLC成人患者的一线治疗。(4)联合蛋白结合型紫杉醇和卡铂用于无EGFR或ALK基因组肿瘤异常的转移性非鳞状NSCLC成人患者的一线治疗。(5)用于治疗接受含铂化疗期间或之后疾病进展的转移性NSCLC成人患者。3. 小细胞肺癌:联合卡铂和依托泊苷用于广泛期小细胞肺癌(ES-SCLC)成人患者的一线治疗。4. 肝细胞癌:联合贝伐珠单抗用于治疗既往未接受系统性治疗的不可切除性或转移性肝细胞癌(HCC)患者。5.黑色素瘤:联合考比替尼和维莫非尼用于治疗BRAF V600突变阳性的不可切除性或转移性黑色素瘤。\\\\PD-L1可能在肿瘤细胞或肿瘤浸润性免疫细胞上表达,并在肿瘤微环境中参与抑制抗肿瘤免疫应答。PD-L1与T细胞和抗原呈递细胞上的PD-1和B7.1受体结合,可抑制细胞毒性T细胞活性、T细胞增殖和细胞因子的产生。阿特珠单抗(Avapritinib)是一种单克隆抗体,可与PD-L1结合并阻断其与PD-1和B7.1受体的相互作用。该作用释放了PD-L1 / PD-1介导的免疫应答抑制作用,激活抗肿瘤免疫应答,且不会引起抗体依赖性细胞毒性。在同系移植小鼠肿瘤模型中,阻断PD-L1活性可降低肿瘤生长。在小鼠癌症模型中,与单独靶向治疗相比,PD-1/PD-L1和MAPK信号通路的双重抑制作用可抑制肿瘤生长,并通过增加抗原呈递和T细胞浸润和激活来改善肿瘤的免疫原性。", - "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。", - "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。", - "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。", - "阿贝西利": "VERZENIO是一种激酶抑制剂,其适应症包括:1.联合内分泌治疗(他莫昔芬/芳香化酶抑制剂)用于性激素受体(HR)阳性、人表皮生长因子受体2(HER2)阴性,淋巴结阳性,高复发风险的早期乳腺癌成年患者的辅助治疗。2.联芳香化酶抑制剂用于治疗激素受体(HR)阳性、人表皮生长因子受体2 (HER2)阴性的晚期或转移性乳腺癌的初期内分泌治疗。3.联合与氟维司群用于激素受体( HR )阳性、人类表皮生长因子受体2 ( HER2 )阴性的晚期或转移性乳腺癌的初始内分泌治疗后疾病进展的治疗。4.单药用于治疗既往接受内分泌治疗后疾病进展的HR阳性、HER2阴性的晚期或转移性乳腺癌成人患者。\\\\BARD1是一种接头蛋白,当与BRCA1结合时具有E3连接酶活性(PMID: 11573085)。BRCA1是一个特征明确的肿瘤抑制因子,其功能是通过同源重组和细胞周期检查点激活来修复DNA双链断裂,从而维持基因组完整性(PMID: 11278247)。BARD1-BRCA1复合物涉及多种细胞进程,包括DNA修复、基因表达、复制叉稳定性维持以及染色质调节的各个阶段(PMID: 27239795)。BARD1与BRCA1相互作用,结合至新复制DNA上的损伤部位,并对组蛋白H2A的赖氨酸残基进行单泛素化修饰(PMID: 30804502)。然后,BARD1-BRCA1复合体介导DNA损伤部位的切除,将拮抗性修复蛋白53BP1驱逐出去,并募集一些DNA损伤反应蛋白(包括RAD51)到受损部位(PMID: 27239795)。聚(ADP-核糖)介导了早期BRCA1-BARD1复合物募集到受损DNA位点的过程(PMID: 25634209)。乳腺癌小鼠模型中BARD1的失活导致了与BRCA1缺失相似的表型,说明BRAD1和BRCA1可能有相似的基因功能(PMID: 18443292)。" - }, - "drugs_type": { - "可能敏感": [ - "达拉非尼", - "康奈非尼", - "维莫非尼", - "Irinotecan", - "贝美替尼", - "考比替尼", - "司美替尼", - "Ipatasertib", - "曲美替尼", - "伏立诺他", - "贝伐珠单抗", - "培唑帕尼", - "阿贝西利" - ], - "可能耐药": [ - "曲美替尼" - ], - "敏感": [ - "康奈非尼", - "贝美替尼", - "西妥昔单抗", - "维莫非尼", - "考比替尼", - "司美替尼", - "阿替利珠单抗", - "帕尼单抗", - "达拉非尼", - "曲美替尼" - ], - "耐药": [ - "达拉非尼", - "EGFR-TKI", - "帕妥珠单抗", - "曲妥珠单抗", - "西妥昔单抗", - "妥卡替尼", - "拉帕替尼", - "EGFR-TKI", - "帕尼单抗", - "trastuzumab deruxtecan" - ] - } - } -} \ No newline at end of file diff --git a/template/~$report.docx 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