[1]姜壮壮,徐婷婷,陶 丽,等.肿瘤KRAS基因突变靶向治疗研究进展[J].中国药理学通报,2019,(10):1346-1349.[doi:10.3969/j.issn.1001-1978.2019.10.004]
 JIANG Zhuang-zhuang,XU Ting-ting,TAO Li,et al.Progress in targeted therapy of tumor KRAS gene mutation[J].Chinese Pharmacological Bulletin,2019,(10):1346-1349.[doi:10.3969/j.issn.1001-1978.2019.10.004]
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肿瘤KRAS基因突变靶向治疗研究进展()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2019年10期
页码:
1346-1349
栏目:
讲座与综述
出版日期:
2019-09-15

文章信息/Info

Title:
Progress in targeted therapy of tumor KRAS gene mutation
文章编号:
1001-1978(2019)10-1346-04
作者:
姜壮壮徐婷婷陶 丽刘延庆
扬州大学医学院,国家中医管理局胃癌毒邪论治重点研究室, 扬州大学医药研究所,扬州大学肿瘤防治重点实验室,江苏 扬州 225001
Author(s):
JIANG Zhuang-zhuang XU Ting-ting TAO Li LIU Yan-qing
Yangzhou University School of Medicine, State Administration of Traditional Chinese Medicine, Key Lab of Treatment of Gastric Cancer Toxin and Pathogen, Institute of Medicine, Yangzhou University, Key Lab of Tumor Prevention and Treatment, Yangzhou University, Yangzhou Jiangsu 225001,China
关键词:
KRAS基因突变 靶向治疗 小干扰RNA 小分子抑制剂 酶活性水平抑制 协同致死
Keywords:
KRAS gene mutation targeted therapy small interfering RNA small molecule inhibitors inhibition of enzyme activity level synergy to death
分类号:
R342.2; R394; R394.2; R730.26; R730.5; R977.6
DOI:
10.3969/j.issn.1001-1978.2019.10.004
文献标志码:
A
摘要:
多数肿瘤伴随KRAS基因突变,并提示不良预后,靶向KRAS突变一直是临床肿瘤治疗的难点。突变的KRAS蛋白难以采用传统抑制活性位点的方式设计特异性抑制剂,被称为“不可靶向的药物靶点”。因此,探索靶向KRAS突变的药物策略成为了肿瘤药物研发的热点。虽然靶向KRAS治疗策略的研究进展有限,但鉴于对KRAS突变功能及恶性机制认识的不断深入,仍出现一些突破性的直接或间接抑制突变KRAS的新策略。该文就目前针对肿瘤KRAS基因突变的靶向治疗的研究进展进行综述,为KRAS突变肿瘤治疗提供新线索。
Abstract:
Targeting KRAS mutations has always been a difficult issue in clinical tumor therapy as most tumors are accompanied by KRAS gene mutations, which indicate poor prognosis.The mutant KRAS protein is difficult to design specific inhibitors in the conventional way of inhibiting the active sites, which is known as “undruggble” target.Therefore, the exploration of drug strategies targeting KRAS mutations has become a hot spot in the research and development of antitumor drugs.Although the research progress of targeted KRAS treatment strategy is limited, some new strategies that directly or indirectly inhibit mutant KRAS are still emerging in view of the deepening understanding of KRAS mutation function and malignant mechanism.In this review, we discussed the research progress of targeted therapy for KRAS gene mutation in tumor, hoping to provide the latest clues for the treatment of KRAS mutant tumor.

参考文献/References:

[1] Kranenburg O.The KRAS oncogene:past, present, and future.Biochim[J].Biochim Biophys Acta, 2005,1756(2):81-2.
[2] 吕莹雪, 刘小玲.KRAS突变非小细胞肺癌的靶向治疗研究进展[J].中南药学, 2018,16(4):513-7.
[2] Lu Y X, Liu X L.Research progress of targeted therapy for non-small cell lung cancer with KRAS mutation[J].Chin Med, 2008,16(4):513-7.
[3] Martin P, Leighl N B, Tsao M S, et al.KRAS mutations as prognostic and predictive markers in non-small cell lung cancer[J].J Thorac Oncol, 2013,8(5):530-42.
[4] Ostrem J M, Peters U, Sos M L, et al.K-Ras(G12C)inhibitors allosterically control GTP affinity and effector interactions[J].Nature, 2013,503(7477), 548-51.
[5] Rui Y, Wang C, Zhou Z, et al.K-Ras mutation and prognosis of colorectal cancer: a meta-analysis[J].Hepatogastroenterology, 2015,62(137): 19-24.
[6] Kempf E, Rousseau B, Besse B, et al.KRAS oncogene in lung cancer: focus on molecularly driven clinical trials[J].Eur Respir Rev, 2016,25(139):71-6.
[7] 王伙刚,洪 波,林文楚.小细胞肺癌靶向治疗研究进展[J].中国药理学通报,2017,33(10):1333-7.
[7] Wang H G, Hong B, Lin W C.Research progress of targeted therapy for small cell lung cancer[J].Chin Pharmacol Bull,2017,33(10):1333-7.
[8] Cao W, Sun J.MicroRNA-200c promotes tumor cell proliferation and migration by directly targeting dachshund family transcription factor 1 by the Wnt/β-catenin signaling pathway in nasopharyngeal carcinoma[J].Anticancer Drugs, 2018,30(3):218-24.
[9] Sun W, Ping W.miR-202 enhances the anti-tumor effect of cisplatin on non-small cell lung cancer by targeting the Ras/MAPK pathway[J].Cell Physiol Biochem, 2018,51(5):2160-71.
[10] Khvalevsky, EZ,Gabai R,Rachmut IH,et al.Mutant KRAS is a druggable target for pancreatic cancer[J].PNAS,2013,11(55):20723-8.
[11] Ramot Y, Rotkopf S, Gabai R M,et al.Preclinical safety evaluation in rats of a polymeric matrix containing an siRNA drug used as a local and prolonged delivery system for pancreatic cancer therapy[J].Toxicol Pathol, 2016,44(6):856-65.
[12] Ross S J, Revenko A S, Hanson L L, et al.Targeting KRAS-dependent tumors with AZD4785, a high-affinity therapeutic antisense oligonucleotide inhibitor of KRAS[J].Sci Transl Med, 2017,9(394):pii: eaal5253.
[13] Ostrem J M, Peters U, Sos M L, et al.KRAS(G12C)inhibitors allosterically control GTP affinity and effector interactions[J].Nature, 2013,503(7477):548-51.
[14] Lim S M, Westover K D, Ficarro S B, et al.Therapeutic tar-geting of oncogenic KRAS by a covalent catalytic site in-hibitor[J].Angew Chem Int Ed Engl, 2014,53(1):199-204.
[15] Patricelli M P, Janes M R, Li L S, et al.Selective inhibition of oncogenic KRAS output with small molecules targeting the inactive state[J].Cancer, 2016,6(3):316-29.
[16] Zimmermann G, Papke B, Ismail S, et al.Small molecule inhibition of the KRAS-PDEdelta interaction impairs oncogenic KRAS signaling[J].Nature, 2013,497(7451):638-42.
[17] Papke B, Murarka S, Vogel H A, et al.Development of pyridazinone chemotypes targeting the PDEδ prenyl binding site[J].Chemistry, 2017,23(25):6083-93.
[18] Steklov M, Pandolfi S, Baietti M F, et al.Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination[J].Science,2018,362(6419):1177-82.
[19] Kim K W, Myers C J, Jung D K,et al.NVP-BEZ-235 enhances radiosensitization via blockade of the PI3K/mTOR pathway in cisplatin-resistant non-small cell lung carcinoma[J].Cancer, 2014,5(7-8):293-302.
[20] 张 卉,杨新杰,秦 娜,等.肺腺癌EGFR与KRAS基因突变状态分析[J].中国肺癌杂志,2015,18(11):686-90.
[20] Zhang H, Yang X J, Qin N, et al.Mutation status analysis of EGFR and KRAS gene in lung adenocarcinoma[J].Chin J Lung Cancer,2015,18(11):686-90.
[21] Manchado E, Weissmueller S, Morris J P, et al.A combinatorial strategy for treating KRAS-mutant lung cancer[J].Nature, 2016,534(7609):647-51.
[22] Dai X, Xia H, Zhou S, et al.Zoledronic acid enhances the efficacy of the MEK inhibitor trametinib in KRAS mutant cancers[J].Cancer Lett, 2019,442:202-12.
[23] Stintzing S, Modest D P, Rossius L, et al.FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer(FIRE-3): a randomised, open-label, phase 3 trial[J].Lancet Oncol, 2014, 15(10):1065-75.
[24] Costa-Cabral S,Brough R, Konde A, et al.CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours[J].2016,11(2):e0149099.
[25] Sharaf L K,Sharma M, Chandel D, et al.Prophylactic intervention of probiotics and celecoxib modulate Bax-mediated apoptosis.in.1,2-dimethylhydrazine-induced experimental colon carcinogenesis[J].BMC Cancer, 2018,18(1):1111.

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备注/Memo

备注/Memo:
收稿日期:2019-06-20,修回日期:2019-08-21 基金项目:国家自然科学基金资助项目(No 81773944,81803782); 江苏省研究生实践创新工程(SJCX19-0900) 作者简介:姜壮壮(1994-),男,硕士生,研究方向:中药抗肿瘤药理学,E-mail:18252773499@163.com; 刘延庆(1956-),男,博士,教授,博士生导师,研究方向:中西医结合肿瘤学,通讯作者,E-mail: liuyq@yzu.edu.cn
更新日期/Last Update: 2019-09-15