切换至 "中华医学电子期刊资源库"

中华结直肠疾病电子杂志 ›› 2020, Vol. 09 ›› Issue (03) : 292 -295. doi: 10.3877/cma.j.issn.2095-3224.2020.03.015

所属专题: 文献

综述

BRAF V600E基因突变在结直肠癌治疗中的研究进展
张祥涛1, 刘睿清1, 张宪祥1,(), 卢云1,()   
  1. 1. 266000 青岛大学附属医院黄岛院区胃肠外二科
  • 收稿日期:2019-11-16 出版日期:2020-06-25
  • 通信作者: 张宪祥, 卢云
  • 基金资助:
    国家自然科学基金青年基金(No.81802473)

Advances in the study of BRAF V600E mutation in the treatment of colorectal cancer

Xiangtao Zhang1, Ruiqing Liu1, Xianxiang Zhang1,(), Yun Lu1,()   

  1. 1. Second Gastrointestinal Department, Huangdao Hospital, Affiliated Hospital of Qingdao University, Qingdao 266000, China
  • Received:2019-11-16 Published:2020-06-25
  • Corresponding author: Xianxiang Zhang, Yun Lu
  • About author:
    Corresponding authors: Lu Yun, Email:
    Zhang Xianxiang, Email:
引用本文:

张祥涛, 刘睿清, 张宪祥, 卢云. BRAF V600E基因突变在结直肠癌治疗中的研究进展[J]. 中华结直肠疾病电子杂志, 2020, 09(03): 292-295.

Xiangtao Zhang, Ruiqing Liu, Xianxiang Zhang, Yun Lu. Advances in the study of BRAF V600E mutation in the treatment of colorectal cancer[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2020, 09(03): 292-295.

结直肠癌是第三大常见癌症,在全球相关癌症死亡率中排名第四。RAS-RAF-MEK-ERK(MAPK)通路的本构性激活在结直肠癌的发生发展中起着重要作用。V-raf鼠肉瘤毒癌基因同源体B(BRAF)是MAPK信号通路上的激酶,在结直肠癌发展中起重要作用。临床观察发现,约8%~10%的结直肠癌病例中存在BRAF V600E突变,并预示较低的中位生存率,对结直肠癌的预后有预测价值。初步探讨BRAF V600E突变,为结直肠癌的分子靶向治疗提供新的思路。

Colorectal cancer is the third most common cancer and the fourth leading cause of cancer-related deaths worldwide. Constitutive activation of Ras-Raf-Mek-Erk (MAPK) pathway plays an important role in the occurrence and development of CRC. V-raf murine sarcoma viral oncogene homolog (BRAF) is a kinase in the MAPK signaling pathway and plays an important role in the development of colorectal cancer. Clinical observations showed that BRAF V600E was found in approximately 8%~10% of CRC cases and was associated with significantly lower median overall survival. It has predictive value for the prognosis of colorectal cancer. A preliminary study on BRAF V600E mutation provides a new idea for molecular targeted therapy of colorectal cancer.

[1]
Das TM, Salangsang F, Landman AS, et al. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance, 2013 [J]. Nature, 2013, 494(7436): 251-255.
[2]
Rizos H, Menzies AM, Pupo GM, et al. BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact, 2014 [J]. Clinical Cancer Research an Official Journal of the American Association for Cancer Research, 2014, 20(7): 1965.
[3]
Nazarian R, Shi H, Wang Q, et al. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation, 2010 [J]. Nature, 2010, 468(7326): 973.
[4]
Prahallad A, Sun C, Huang S, et al. Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR, 2012 [J]. Nature, 2012, 483(7387): 100.
[5]
Yang H, Higgins B, Kolinsky K, et al. Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer, 2012 [J]. Cancer Research, 2012, 72(3): 779.
[6]
Walther A, Johnstone E, Swanton C, et al. Genetic prognostic and predictive markers in colorectal cancer, 2009 [J]. Nat Rev Cancer, 2009, 9: 489-499.
[7]
Ewing I, Hurley JJ, Josephides E, et al. The molecular genetics of colorectal cancer, 2014 [J]. Frontline Wastroenterol, 2014, 5(1): 26-30.
[8]
Sameer AS, Nissar S, Fatima K. Mismatch repair pathway: molecules, functions, and role in colorectal carcinogenesis, 2014 [J]. Eur J Cancer Prev, 2014, 23(4): 246-257.
[9]
Lengauer C, Kinzler KW, Vogelstein B, et al. Genetic instability in colorectal cancers, 1997 [J]. Nature, 1997, 386: 623-627.
[10]
Gordon DJ, Resio B, Pellman D, et al. Causes and consequences of aneuploidy in cancer, 2012 [J]. Nat Rev Genet, 2012, 13: 189-203.
[11]
Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features, 2007 [J]. Histopathology, 2007, 50: 113-130.
[12]
Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer, 2006 [J]. Nat Genet, 2006, 38: 787-793.
[13]
Jass JR, Do KA, Simms LA, et al. Morphology of sporadic colorectal cancer with DNA replication errors, 1998 [J]. Gut, 1998, 42: 673-679.
[14]
Walther A, Houlston R, Tomlinson I, et al. Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis, 2008 [J]. Gut, 2008, 57: 941-950.
[15]
Watanabe T, Kobunai T, Yamamoto Y, et al. Chromosomal instability(CIN) phenotype, CIN high or CIN low, predicts survival for colorectal cancer, 2012 [J]. J Clin Oncol, 2012, 30(18): 2256-2264.
[16]
Sinicrope FA, Rego RL, Halling KC, et al. Prognostic impact of microsatellite instability and DNA ploidy in human colon carcinoma patients, 2006 [J]. Gastroenterology, 2006, 131: 729-737.
[17]
Popat S, Hubner R, Houlston RS, et al. Systematic review of microsatellite instability and colorectal cancer prognosis, 2005 [J]. J Clin Oncol, 2005, 23: 609-618.
[18]
Sinicrope FA, Foster NR, Thibodeau SN, et al. DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy, 2011 [J]. J Natl Cancer Inst, 2011, 103: 863-875.
[19]
Müller CI, Schulmann K, Reinacher-Schick A, et al. Predictive and prognostic value of microsatellite instability in patients with advanced colorectal cancer treated with a fluoropyrimidine and oxaliplatin containing first-line chemotherapy. A report of the AIO Colorectal Study Group, 2008 [J]. Int J Colorectal Dis, 2008, 23: 1033-1039.
[20]
Samowitz WS, Sweeney C, Herrick J, et al. Poor survival associated with the BRAF V600E mutation in microsatellite-stable colon cancers, 2005 [J]. Cancer Res, 2005, 65: 6063-6069.
[21]
Ogino S, Shima K, Meyerhardt J, et al. Predictive and prognostic roles of BRAF mutation in stage III colon cancer: results from intergroup trial CALGB 89803, 2012 [J]. Clin Cancer Res, 2012, 18(3): 890-900.
[22]
Bond CE, Nancarrow DJ, Wockner LF, et al. Microsatellite stable colorectal cancers stratified by the BRAF V600E mutation show distinct patterns of chromosomal instability [J]. PLoS ONE, 2014, 9(3): e91739.
[23]
Koinuma K, Shitoh K, Miyakura Y, et al. Mutations of BRAF are associated with extensive hMLH1 promoter methylation in sporadic colorectal carcinomas, 2004 [J]. Int J Cancer, 2004, 108: 237-242.
[24]
Sérgia V, Cátia M, Luís C, et al. BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: Primary or secondary genetic events in colorectal carcinogenesis, 2008 [J]. BMC Cancer, 2008, 8: 255.
[25]
Riccio A, Aaltonen LA, Godwin AK, et al. The DNA repair gene MBD4 (MED1) is mutated in human carcinomas with microsatellite instability, 1999 [J]. Nature Genetics, 1999, 23(3): 266-268.
[26]
Tricarico R, Cortellino S, Riccio A, et al. Involvement of MBD4 inactivation in mismatch repair-deficient tumorigenesis, 2015 [J]. Oncotarget, 2015, 6(40): 42892.
[27]
Toyota M, Ahuja N, Ohe-Toyota M, et al. CpG island methylator phenotype in colorectal cancer, 1999 [J]. Proc Nati Acad Sci USA, 1999, 96: 8681-8686.
[28]
孙乃恩,孙东旭,朱德煦. 分子遗传学[M]. 南京: 南京大学出版社, 2001.
[29]
O′Brien MJ. Hyperplastic and serrated polyps of the colorectum, 2007 [J]. Gastroenterol Clin North Am, 2007, 36: 947-968,viii.
[30]
Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype underlies sporadic microsatellite instabilityand is tightly associated with BRAF mutation in colorectal cancer, 2006 [J]. Nat Genet, 2006, 38: 787-793.
[31]
Samowitz WS, Albertsen H, Herrick J, et al. Evaluation of a large, population-based sample supports a CpG islandmethylator phenotype in colon cancer, 2005 [J]. Gastroenterology, 2005, 129: 837-845.
[32]
Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer [J]. Nat Genet, 2006, 38(7): 787-793.
[33]
Kambara T, SimmsL A, Whitehall VL, et al. BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum, 2004 [J]. Gut, 2004, 53(8): 1137-1144.
[34]
Minoo P, Moyer MP, Jass JR. Role of BRAF-V600E in the serrated pathway of colorectal tumourigenesis, 2007 [J]. Journal of Pathology, 2007, 212(2): 124-133.
[35]
Si L, Kong Y, Xu X, et al. Prevalence of BRAF V600E mutation in Chinese melanoma patients: Large scale analysis of BRAF and NRAS mutations in a 432-case cohort, 2012 [J]. European Journal of Cancer, 2012, 48(1): 94-100.
[36]
Santarpia L, Lippman SM, Elnaggar AK. Targeting the MAPK-RAS-RAF signaling pathway in cancer therapy, 2012 [J]. Expert Opinion on Therapeutic Targets, 2012, 16(1): 103-119.
[37]
Wan PT, Garnett MJ, Roe SM, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF, 2004 [J]. Cell, 2004, 116: 855-867.
[38]
Xiong J, He M, Hansen K, et al. The clinical significance of K-ras mutation in endometrial "surface epithelial changes" and their associated endometrial adenocarcinoma, 2016 [J]. Gynecol Oncol, 2016, 142: 163-168.
[39]
Hertzman Johansson C, Egyhazi Brage S. BRAF inhibitors in cancer therapy, 2014 [J]. Pharmacol Ther, 2014, 142: 176-182.
[40]
Fang M, Ou J, Hutchinson L, et al. The BRAF oncoprotein functions through the transcriptional repressor MAFG to mediate the CpG island methylator phenotype, 2014 [J]. Molecular Cell, 2014, 55(6): 904-915.
[41]
Martín Martorell P, Huerta M, Compañ Quilis A, et al. Coexistence of EGFR, KRAS, BRAF, and PIK3CA mutations and ALK rearrangement in a comprehensive cohort of 326 consecutive Spanish nonsquamous NSCLC patients, 2017 [J]. Clin Lung Cancer, 2017, 18(6): e395-e402.
[42]
宋敏,孙亚琼,张莉,等. 结直肠癌组织KRAS和BRAF基因突变情况及意义[J]. 山东医药, 2014, (32): 32-34.
[43]
Di Nicolantonio F, Martini M, Molinari F, et al. Wild-type BRAF is required for response to panitumumabor cetuximab in metastatic colorectal cancer, 2008 [J]. J Clin Oncol, 2008, 26(35): 5705-5712.
[44]
Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated, activated BRAF in metastatic melanoma, 2010 [J]. N Engl J Med, 2010, 363(9): 809-819.
[45]
Long GV, Stroyakovskiy D, Gogas H, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma, 2014 [J]. N Engl J Med, 2014, 371(20): 1877-1888.
[46]
Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain, 2005 [J]. PLoS Med, 2005, 2(3): e73.
[47]
Kopetz S, Desai J, Chan E, et al. Phase Ⅱ pilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer, 2015 [J]. J Clin Oncol, 2015, 33(34): 4032-4038.
[48]
Corcoran RB, Atreya CE, Falchook GS, et al. Combined BRAF and MEK inhibition with dabrafenib and trametinib in BRAF V600-Mutant colorectal cancer [J]. J Clin Oncol, 2015, 33(34): 4023-4031.
[49]
Kopetz S, McDonough SL, Morris VK, et al. Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG 1406), 2017 [J]. J Clin Oncol, 2017, 35: 520.
[50]
Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, binimetinib, and cetuximab in V600E-mutated colorectal cancer.N, 2015 [J]. Engl J Med, 2015,10.1056/NEJMoa1908075.
[51]
Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency, 2015 [J]. JN Engl J Med, 2015, 372(26): 2509-2520.
[1] 康夏, 田浩, 钱进, 高源, 缪洪明, 齐晓伟. 骨织素抑制破骨细胞分化改善肿瘤骨转移中骨溶解的机制研究[J]. 中华乳腺病杂志(电子版), 2023, 17(06): 329-339.
[2] 马敏榕, 李聪, 周勤. 宫颈癌治疗研究现状[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 497-504.
[3] 林昌盛, 战军, 肖雪. 上皮性卵巢癌患者诊疗中基因检测及分子靶向药物治疗[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 505-510.
[4] 代莉, 邓恢伟, 郭华静, 黄芙蓉. 术中持续输注艾司氯胺酮对腹腔镜结直肠癌手术患者术后睡眠质量的影响[J]. 中华普通外科学文献(电子版), 2023, 17(06): 408-412.
[5] 王得晨, 杨康, 杨自杰, 归明彬, 屈莲平, 张小凤, 高峰. 结直肠癌微卫星稳定状态和程序性死亡、吲哚胺2,3-双加氧酶关系的研究进展[J]. 中华普通外科学文献(电子版), 2023, 17(06): 462-465.
[6] 唐旭, 韩冰, 刘威, 陈茹星. 结直肠癌根治术后隐匿性肝转移危险因素分析及预测模型构建[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 16-20.
[7] 张生军, 赵阿静, 李守博, 郝祥宏, 刘敏丽. 高糖通过HGF/c-met通路促进结直肠癌侵袭和迁移的实验研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 21-24.
[8] 李婷, 张琳. 血清脂肪酸代谢物及维生素D水平与结直肠癌发生的关系研究[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 661-665.
[9] 魏小勇. 原发性肝癌转化治疗焦点问题探讨[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 602-607.
[10] 吴晨瑞, 廖锐, 贺强, 潘龙, 黄平, 曹洪祥, 赵益, 王永琛, 黄俊杰, 孙睿锐. MDT模式下肝动脉灌注化疗联合免疫靶向治疗肝细胞癌多处转移一例[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 713-716.
[11] 倪文凯, 齐翀, 许小丹, 周燮程, 殷庆章, 蔡元坤. 结直肠癌患者术后发生延迟性肠麻痹的影响因素分析[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 484-489.
[12] 范小彧, 孙司正, 鄂一民, 喻春钊. 梗阻性左半结肠癌不同手术治疗方案的选择应用[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 500-504.
[13] 关旭, 王锡山. 基于外科与免疫视角思考结直肠癌区域淋巴结处理的功与过[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 448-452.
[14] 顾睿祈, 方洪生, 蔡国响. 循环肿瘤DNA检测在结直肠癌诊治中的应用与进展[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 453-459.
[15] 孙昕, 程海波, 沈卫星. 基于全转录组学探讨仙连解毒方治疗Ⅲ期结直肠癌患者的疗效机制[J]. 中华消化病与影像杂志(电子版), 2023, 13(05): 277-283.
阅读次数
全文


摘要