国际口腔医学杂志

国际口腔医学杂志 ›› 2021, Vol. 48 ›› Issue (6): 731-736.doi: 10.7518/gjkq.2021094

• 综述 • 上一篇    下一篇

涎腺导管癌PI3K/AKT/mTOR信号通路中高频突变基因的研究进展

柴国超(),张素欣()   

  1. 河北医科大学第四医院口腔科 石家庄 050011
  • 收稿日期:2021-01-06 修回日期:2021-06-14 出版日期:2021-11-01 发布日期:2021-10-28
  • 通讯作者: 张素欣
  • 作者简介:柴国超,医师,硕士,Email： 1240862836@qq.com
  • 基金资助:
    河北省卫生健康委员会重点科技研究计划(20190695)

Research progress on high-frequency mutated genes in the PI3K/AKT/mTOR signalling pathway in salivary duct carcinoma

Chai Guochao(),Zhang Suxin()   

  1. Dept. of Stomatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China
  • Received:2021-01-06 Revised:2021-06-14 Online:2021-11-01 Published:2021-10-28
  • Contact: Suxin Zhang
  • Supported by:
    Key Science and Technology Research Program of Hebei Provincial Health Commission(20190695)

RichHTML

19

PDF (PC)

528

摘要：

涎腺导管癌（SDC）是涎腺癌的1种侵袭性亚型,复发和转移率高。传统治疗方案是手术切除+淋巴结清扫+辅助放疗,预后较差。近年来,第2代基因测序（NGS）和免疫组织化学（IHC）技术高速发展。借助NGS和IHC技术在SDC中发现多种高频突变基因,这些突变基因以PI3K/AKT/mTOR信号通路为主要靶向信号节点,对SDC产生生物学效应。本文通过对PI3K/AKT/mTOR信号通路及其高频突变基因的介绍进行综述,阐述SDC发生、发展的分子机制。

关键词: 涎腺导管癌, 突变基因, 靶点

Abstract:

Salivary duct carcinoma (SDC) is an aggressive subtype of salivary gland carcinoma with high recurrence and metastasis rates. The traditional treatment is surgical resection, lymph node dissection and adjuvant radiotherapy, and the prognosis is poor. In recent years, second-generation gene sequencing (NGS) and immunohistochemistry (IHC) technology have developed rapidly. High-frequency mutant genes were found in SDC by NGS and IHC. These mutant genes have biological effects on SDC with the PI3K/AKT/mTOR signalling pathway as the main target signal node. The author intends to summarise the PI3K/AKT/mTOR signalling pathway and its high-frequency mutant genes, as well as elaborate the molecular mechanism of the occurrence and development of SDC.

Key words: salivary duct carcinoma, mutant genes, target

中图分类号: 

  • R780.2
[1] Seethala RR, Stenman G. Update from the 4th edition of the world health organization classification of head and neck tumours: tumors of the salivary gland[J]. Head Neck Pathol, 2017, 11(1):55-67.
doi: 10.1007/s12105-017-0795-0 pmid: 28247227
[2] Jayaprakash V, Merzianu M, Warren GW, et al. Survival rates and prognostic factors for infiltrating salivary duct carcinoma: analysis of 228 cases from the surveillance, epidemiology, and end results database[J]. Head Neck, 2014, 36(5):694-701.
doi: 10.1002/hed.v36.5
[3] Osborn V, Givi B, Lee A, et al. Characterization, treatment and outcomes of salivary ductal carcinoma using the National Cancer Database[J]. Oral Oncol, 2017, 71:41-46.
doi: 10.1016/j.oraloncology.2017.05.005
[4] Dalin MG, Desrichard A, Katabi N, et al. Comprehensive molecular characterization of salivary duct carcinoma reveals actionable targets and similarity to apocrine breast cancer[J]. Clin Cancer Res, 2016, 22(18):4623-4633.
doi: 10.1158/1078-0432.CCR-16-0637
[5] 何时, 何同梅, 卢建平, 等. 31例涎腺导管癌的临床病理分析[J]. 临床与病理杂志, 2019, 39(7):41-49.
He S, He TM, Lu JP, et al. Clinicopathologic fea-tures of 31 cases of salivary duct carcinoma[J]. Int J Path Clin Med, 2019, 39(7):41-49.
[6] Kleinsasser O, Klein HJ, Hübner G. Salivary duct carcinoma. A group of salivary gland tumors analogous to mammary duct carcinoma[J]. Arch Klin Exp Ohren Nasen Kehlkopfheilkd, 1968, 192(1):100-105.
pmid: 4301301
[7] Luk PP, Weston JD, Yu B, et al. Salivary duct carcinoma: clinicopathologic features, morphologic spectrum, and somatic mutations[J]. Head Neck, 2016, 38(Suppl 1):E1838-E1847.
doi: 10.1002/hed.24332
[8] Enomoto T, Aoki M, Miyagawa K, et al. A case of salivary duct carcinoma intracranial invasion due to perineural invasion through the facial nerve[J]. World Neurosurg, 2020, 140:332-337.
doi: 10.1016/j.wneu.2020.05.180
[9] Wu WL, Wang CL, Li D, et al. Multiphase contrast-enhanced computed tomography imaging features of salivary duct carcinoma: differentiation from other salivary gland malignancies[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2019, 128(5):543-551.
doi: 10.1016/j.oooo.2019.05.011
[10] 李子园, 管民, 窦社伟, 等. 涎腺导管癌CT及MRI影像特征分析[J]. 中华实用诊断与治疗杂志, 2021, 35(2):181-184.
Li ZY, Guan M, Dou SW, et al. CT and MRI features of salivary duct carcinoma[J]. J Chin Pract Diagn Ther, 2021, 35(2):181-184.
[11] Nakaguro M, Sato Y, Tada Y, et al. Prognostic implication of histopathologic indicators in salivary duct carcinoma: proposal of a novel histologic risk stratification model[J]. Am J Surg Pathol, 2020, 44(4):526-535.
doi: 10.1097/PAS.0000000000001413 pmid: 31764219
[12] Pfister DG, Spencer S, Adelstein D, et al. Head and neck cancers, version 2.2020, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2020, 18(7):873-898.
doi: 10.6004/jnccn.2020.0031
[13] Alame M, Cornillot E, Cacheux V, et al. The mole-cular landscape and microenvironment of salivary duct carcinoma reveal new therapeutic opportunities[J]. Theranostics, 2020, 10(10):4383-4394.
doi: 10.7150/thno.42986
[14] Gargano SM, Senarathne W, Feldman R, et al. No-vel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling[J]. Cancer Med, 2019, 8(17):7322-7329.
doi: 10.1002/cam4.v8.17
[15] Wang K, Russell JS, McDermott JD , et al. Profiling of 149 salivary duct carcinomas, carcinoma ex pleomorphic adenomas, and adenocarcinomas, not otherwise specified reveals actionable genomic alterations[J]. Clin Cancer Res, 2016, 22(24):6061-6068.
pmid: 27334835
[16] Aoki M, Fujishita T. Oncogenic roles of the PI3K/AKT/mTOR axis[J]. Curr Top Microbiol Immunol, 2017, 407:153-189.
[17] Takács T, Kudlik G, Kurilla A, et al. The effects of mutant Ras proteins on the cell signalome[J]. Cancer Metastasis Rev, 2020, 39(4):1051-1065.
doi: 10.1007/s10555-020-09912-8
[18] Xu F, Na LX, Li YF, et al. Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative di-seases and tumours[J]. Cell Biosci, 2020, 10:54.
doi: 10.1186/s13578-020-00416-0
[19] Ettl T, Schwarz-Furlan S, Haubner F, et al. The PI3K/AKT/mTOR signalling pathway is active in salivary gland cancer and implies different functions and pro-gnoses depending on cell localisation[J]. Oral Oncol, 2012, 48(9):822-830.
doi: 10.1016/j.oraloncology.2012.02.021
[20] Tewari D, Patni P, Bishayee A, et al. Natural pro-ducts targeting the PI3K-Akt-mTOR signaling pathway in cancer: a novel therapeutic strategy[J]. Se-min Cancer Biol, 2019: S1044- S579X(19)30405-5.
[21] Suzuki S, Dobashi Y, Minato H, et al. EGFR and HER2-Akt-mTOR signaling pathways are activated in subgroups of salivary gland carcinomas[J]. Virchows Arch, 2012, 461(3):271-282.
doi: 10.1007/s00428-012-1282-3
[22] Oh DY, Bang YJ. HER2-targeted therapies-a role beyond breast cancer[J]. Nat Rev Clin Oncol, 2020, 17(1):33-48.
doi: 10.1038/s41571-019-0268-3
[23] Santana T, Pavel A, Martinek P, et al. Biomarker immunoprofile and molecular characteristics in saliva-ry duct carcinoma: clinicopathological and prognostic implications[J]. Hum Pathol, 2019, 93:37-47.
doi: 10.1016/j.humpath.2019.08.009
[24] Williams MD, Roberts DB, Kies MS, et al. Genetic and expression analysis of HER-2 and EGFR genes in salivary duct carcinoma: empirical and therapeutic significance[J]. Clin Cancer Res, 2010, 16(8):2266-2274.
doi: 10.1158/1078-0432.CCR-09-0238
[25] Valabrega G, Montemurro F, Aglietta M. Trastuzu-mab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer[J]. Ann Oncol, 2007, 18(6):977-984.
pmid: 17229773
[26] Hanna GJ, Bae JE, Lorch JH, et al. The benefits of adjuvant trastuzumab for HER-2-positive salivary gland cancers[J]. Oncologist, 2020, 25(7):598-608.
doi: 10.1634/theoncologist.2019-0841
[27] Takahashi H, Tada Y, Saotome T, et al. PhaseⅡtrial of trastuzumab and docetaxel in patients with human epidermal growth factor receptor 2-positive sa-livary duct carcinoma[J]. J Clin Oncol, 2019, 37(2):125-134.
doi: 10.1200/JCO.18.00545 pmid: 30452336
[28] Limaye SA, Posner MR, Krane JF, et al. Trastuzu-mab for the treatment of salivary duct carcinoma[J]. Oncologist, 2013, 18(3):294-300.
doi: 10.1634/theoncologist.2012-0369
[29] Arafeh R, Samuels Y. PIK3CA in cancer: the past 30 years[J]. Semin Cancer Biol, 2019, 59:36-49.
doi: S1044-579X(18)30152-4 pmid: 30742905
[30] Qiu WL, Tong GX, Turk AT, et al. Oncogenic PIK-3CA mutation and dysregulation in human salivary duct carcinoma[J]. Biomed Res Int, 2014, 2014:81-0487.
[31] Griffith CC, Seethala RR, Luvison A, et al. PIK3CA mutations and PTEN loss in salivary duct carcinomas[J]. Am J Surg Pathol, 2013, 37(8):1201-1207.
doi: 10.1097/PAS.0b013e3182880d5a
[32] Nardi V, Sadow PM, Juric D, et al. Detection of no-vel actionable genetic changes in salivary duct carcinoma helps direct patient treatment[J]. Clin Cancer Res, 2013, 19(2):480-490.
doi: 10.1158/1078-0432.CCR-12-1842
[33] Juric D, Rodon J, Tabernero J, et al. Phosphatidy-linositol 3-kinase α-selective inhibition with alpeli-sib (BYL719) in PIK3CA-altered solid tumors: results from the first-in-human study[J]. J Clin Oncol, 2018, 36(13):1291-1299.
doi: 10.1200/JCO.2017.72.7107
[34] Saintigny P, Mitani Y, Pytynia KB, et al. Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in salivary duct carcinoma: implications for targeted therapy[J]. Cancer, 2018, 124(18):3693-3705.
doi: 10.1002/cncr.31600 pmid: 30289966
[35] Arolt C, Meyer M, Ruesseler V, et al. Lymphocyte activation gene 3 (LAG3) protein expression on tumor-infiltrating lymphocytes in aggressive and TP53-mutated salivary gland carcinomas[J]. Cancer Immunol Immunother, 2020, 69(7):1363-1373.
doi: 10.1007/s00262-020-02551-6
[36] Luk PP, Weston JD, Yu B, et al. Salivary duct carcinoma: clinicopathologic features, morphologic spectrum, and somatic mutations[J]. Head Neck, 2016, 38(Suppl 1):E1838-E1847.
doi: 10.1002/hed.24332
[37] Fu Y, Cruz-Monserrate Z, Helen Lin H, et al. Ductal activation of oncogenic KRAS alone induces sarcomatoid phenotype[J]. Sci Rep, 2015, 5:13347.
doi: 10.1038/srep13347
[38] Athuluri-Divakar SK, Vasquez-Del Carpio R, Dutta K , et al. A small molecule RAS-mimetic disrupts RAS association with effector proteins to block signaling[J]. Cell, 2016, 165(3):643-655.
doi: 10.1016/j.cell.2016.03.045 pmid: 27104980
[39] Spencer-Smith R, Koide A, Zhou Y, et al. Inhibition of RAS function through targeting an allosteric regulatory site[J]. Nat Chem Biol, 2017, 13(1):62-68.
doi: 10.1038/nchembio.2231 pmid: 27820802
[40] Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: origins, consequences, and clinical use[J]. Cold Spring Harb Perspect Biol, 2010, 2(1):a001008.
[41] Abraham AG, O’Neill E . PI3K/Akt-mediated regulation of p53 in cancer[J]. Biochem Soc Trans, 2014, 42(4):798-803.
doi: 10.1042/BST20140070
[42] Carracedo A, Alimonti A, Pandolfi PP. PTEN level in tumor suppression: how much is too little[J]. Cancer Res, 2011, 71(3):629-633.
doi: 10.1158/0008-5472.CAN-10-2488 pmid: 21266353
[43] Gharbi SI, Zvelebil MJ, Shuttleworth SJ, et al. Exploring the specificity of the PI3K family inhibitor LY294002[J]. Biochem J, 2007, 404(1):15-21.
doi: 10.1042/BJ20061489
[44] Ettl T, Baader K, Stiegler C, et al. Loss of PTEN is associated with elevated EGFR and HER2 expression and worse prognosis in salivary gland cancer[J]. Br J Cancer, 2012, 106(4):719-726.
doi: 10.1038/bjc.2011.605
[1] 韩冲,何东宁,余飞燕,吴东潮. 口腔种植术后疼痛机制及治疗的研究进展[J]. 国际口腔医学杂志, 2024, 51(1): 99-106.
[2] 胡晓文. 端粒G-四联体——肿瘤治疗的新靶点[J]. 国际口腔医学杂志, 2004, 31(S1): -.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] 王昆润. 二甲亚砜和双氯芬酸并用治疗根尖周炎[J]. 国际口腔医学杂志, 1999, 26(06): .
[2] 汤庆奋,王学侠. 17β-雌二醇对人类阴道和口腔颊粘膜的渗透性[J]. 国际口腔医学杂志, 1999, 26(06): .
[3] 潘劲松. 颈总动脉指压和颈内动脉球囊阻断试验在大脑血液动力学中的不同影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[4] 王昆润. 后牙冠根斜形牙折的治疗[J]. 国际口腔医学杂志, 1999, 26(05): .
[5] 杨锦波. 嵌合体防龋疫苗的研究进展[J]. 国际口腔医学杂志, 1999, 26(05): .
[6] 王昆润. 下颔骨成形术用网状钛板固定植骨块[J]. 国际口腔医学杂志, 1999, 26(04): .
[7] 汪月月,郭莉莉. 口腔机能与老化—痴呆危险因素流行病学研究[J]. 国际口腔医学杂志, 1999, 26(04): .
[8] 丁刚. 应用硬组织代用品种植体行丰颏术[J]. 国际口腔医学杂志, 1999, 26(04): .
[9] 田磊. 局部应用脂多糖后结合上皮反应性增生的变化[J]. 国际口腔医学杂志, 1999, 26(04): .
[10] 戴青. 口腔念珠菌病的新分类[J]. 国际口腔医学杂志, 1999, 26(04): .