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中华口腔医学研究杂志(电子版) ›› 2019, Vol. 13 ›› Issue (05) : 257 -264. doi: 10.3877/cma.j.issn.1674-1366.2019.05.001

所属专题： 口腔医学； 文献；

中青年专家笔谈

PI3K/Akt/mTOR通路在头颈部鳞状细胞癌中的靶向治疗研究进展
邢益菡1, 李卓盈1, 许宝山1,†()   
  1. 1. 中山大学光华口腔医学院·附属口腔医院，广东省口腔医学重点实验室，广州　510055
  • 收稿日期:2019-09-02 出版日期:2019-10-01
  • 通信作者: 许宝山

PI3K/Akt/mTOR signaling pathway on targeted therapies of head and neck squamous cell carcinoma

Yihan Xing1, Zhuoying Li1, Baoshan Xu1,†()   

  1. 1. Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China
  • Received:2019-09-02 Published:2019-10-01
  • Corresponding author: Baoshan Xu
  • About author:
    Corresponding author: Xu Baoshan, Email:
  • Supported by:
    National Natural Science Foundation of China(81771056, 81972533); The project is supported by Special Funds for the Cultivation of Guangdong College Students′ Scientific and Technological Innovation("Climbing Program" Special Funds pdjh2019b0016); Sun Yat-sen University 2019 Undergraduate Innovation and Entrepreneurship Training Program(201901246)
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邢益菡, 李卓盈, 许宝山. PI3K/Akt/mTOR通路在头颈部鳞状细胞癌中的靶向治疗研究进展[J]. 中华口腔医学研究杂志(电子版), 2019, 13(05): 257-264.

Yihan Xing, Zhuoying Li, Baoshan Xu. PI3K/Akt/mTOR signaling pathway on targeted therapies of head and neck squamous cell carcinoma[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2019, 13(05): 257-264.

头颈部鳞状细胞癌（HNSCC）在全球最常见的恶性肿瘤中位居第六，晚期患者转移并复发率高，预后较差，为患者家庭和社会经济带来严重损失。靶向药物结合经典放化疗的个性化方案有望提高治疗功效并延长生存期。磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白（PI3K/Akt/mTOR）在HNSCC中普遍存在过度激活，是控制肿瘤发生、发展及研发靶向药物的重要通路。本文就PI3K/Akt/mTOR通路应用于HNSCC靶向治疗的个体性差异发生的潜在机制，以及临床试验取得的进展与目前所面临的困境进行探讨，拟为HNSCC的临床靶向治疗提供参考思路，从而提高患者的生存质量。

关键词: 头颈部肿瘤, 癌，鳞状细胞, 分子靶向治疗, PI3K/Akt/mTOR信号通路

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause for cancer-related mortality worldwide. Personalized medicine of targeted drugs combined with classical radiotherapy and chemotherapy after surgery is expected to improve therapeutic efficacy and prolong survival rate of patients. It is known that increasing activation of PI3K/Akt/mTOR signaling pathway in HNSCC plays a central role to drive tumorigenesis and cancer metastasis. This article will explore the potential molecular mechanisms of individual differences in PI3K/Akt/mTOR signaling pathway applied in targeted therapy, the progress and current dilemmas of clinical trials, to provide a scheme for clinical treatment strategies to improve the life quality of the patients.

Key words: Head and neck neoplasms, Carcinoma, squamous cell, Molecular targeted therapy, PI3K/Akt/mTOR signaling pathway
图1 PI3K/Akt/mTOR信号通路及其在头颈部鳞状细胞癌（HNSCC）中的药物靶点
表1 HNSCC临床试验阶段靶向药物研究进展（clinicaltrials.gov）
药物 试验编码 阶段 使用方法 受试群体
EGFR抑制剂 ? ? ? ?
? 西妥昔单抗 NCT00468169 Ⅱ 分别联合5-氟尿嘧啶、羟基脲、放疗和顺铂、放疗 Ⅲ、Ⅳ期头颈部鳞状细胞癌
NCT00409565 Ⅱ 联合贝伐单抗 复发和转移头颈部鳞状细胞癌
NCT02110082 Ⅰb 联合乌鲁单抗(Urelumab) 晚期和转移头颈部鳞状细胞癌
? 帕尼单抗 NCT00500760 Ⅱ 联合顺铂 局部晚期头颈部鳞状细胞癌
NCT03733210 Ⅰ 单药 头颈部鳞状细胞癌
NCT02415881 Ⅰ 单药 头颈部鳞状细胞癌
? 厄洛替尼 NCT00570232 Ⅱ 单药 复发性头颈部鳞状细胞癌
NCT00942734 Ⅱ 联合依维莫司 复发性头颈部鳞状细胞癌
NCT00970502 Ⅰ/Ⅱ 联合塞来昔布 头颈部鳞状细胞癌
? 吉非替尼 NCT00519077 Ⅱ 单药 复发和转移头颈部鳞状细胞癌
? 阿法替尼 NCT02979977 Ⅱ 联合西妥昔单抗 局部晚期、复发和转移头颈部鳞状细胞癌
NCT01824823 Ⅱ 单药 Ⅲ、Ⅳ期头颈部鳞状细胞癌
NCT01345682 Ⅲ 单药 复发和转移头颈部鳞状细胞癌
? 拉帕提尼 NCT00387127 Ⅱ 联合顺铂、放疗 头颈部鳞状细胞癌
NCT00424255 Ⅲ 联合放化疗 Ⅱ、Ⅲ、Ⅳa期头颈部鳞状细胞癌
VEGFR抑制剂 ? ? ? ?
? 贝伐珠单抗 NCT00409565 Ⅱ 联合西妥昔单抗 复发和转移头颈部鳞状细胞癌
NCT00423930 Ⅱ 联合顺铂、放疗 Ⅲ、Ⅳ期头颈部鳞状细胞癌
NCT00222729 Ⅱ 联合培美曲塞 复发和转移头颈部鳞状细胞癌
? 福林替尼 NCT00725764 Ⅱ 单药 复发和转移头颈部鳞状细胞癌
IGFR抑制剂 ? ? ? ?
? Cixutumumab NCT00617734 Ⅱ 单药或联合西妥昔单抗 复发和转移头颈部鳞状细胞癌
FGFR抑制剂 ? ? ? ?
? Infigratinib NCT02706691 Ⅱ 单药 存在FGFR1-3基因改变的头颈部鳞状细胞癌
? Rogaratinib NCT01976741 Ⅰ 单药 局部晚期和转移实体瘤
PDGFR抑制剂 ? ? ? ?
? 伊马替尼 NCT00485485 Ⅱ 联合紫杉醇 复发和转移头颈部鳞状细胞癌
PI3K抑制剂 ? ? ? ?
? Alpelisib NCT02537223 Ⅰ 联合顺铂、放化疗 局部晚期头颈部鳞状细胞癌
NCT02145312 Ⅱ 单药 复发和转移头颈部鳞状细胞癌
NCT02051751 Ⅰb 联合紫杉醇 复发和转移头颈部鳞状细胞癌
? Buparlisib NCT02113878 Ⅰb 联合顺铂、放化疗 Ⅲ、Ⅳ期头颈部鳞状细胞癌
? Gedatolisib NCT03065062 Ⅰ 联合哌柏西利(Palbociclib，PD-0332991) 晚期肺、胰腺、头颈部鳞状细胞瘤及其他实体瘤
Akt抑制剂 ? ? ? ?
? MK-2206 NCT01349933 Ⅱ 单药 Ⅳ期、复发鼻咽鳞状细胞癌
mTOR抑制剂 ? ? ? ?
? 雷帕霉素 NCT01283334 Ⅰ/Ⅱb 联合卡铂、西妥昔单抗、依维莫司 复发和转移头颈部鳞状细胞癌
NCT00942734 Ⅱ 联合厄洛替尼 复发性头颈部鳞状细胞癌
? 坦西莫司 NCT01016769 Ⅰ/Ⅱ 联合紫杉醇、卡铂 复发和转移头颈部鳞状细胞癌
NCT01256385 Ⅱ 联合西妥昔单抗 复发和转移头颈部鳞状细胞癌
? 依维莫司 NCT03578432 Ⅰ 单药 放化疗后局部晚期头颈部鳞状细胞癌
NCT00942734 Ⅱ 联合厄洛替尼 复发性头颈部鳞状细胞癌
[1]
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018：GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin，2018，68(6): 394-424. DOI: 10.3322/caac.21492.
[2]
von Mehren M, Randall RL, Benjamin RS, et al. Soft Tissue Sarcoma，Version 2.2018，NCCN Clinical Practice Guidelines in Oncology[J]. J Natl Compr Canc Netw，2018，16(5): 536-563. DOI: 10.6004/jnccn.2018.0025.
[3]
中国临床肿瘤学会指南工作委员会.中国临床肿瘤学会（CSCO）头颈部肿瘤诊疗指南[M].北京：人民卫生出版社，2018.
[4]
Martins RG, Parvathaneni U, Bauman JE, et al. Cisplatin and Radiotherapy With or Without Erlotinib in Locally Advanced Squamous Cell Carcinoma of the Head and Neck：A Randomized Phase II Trial[J]. J Clin Oncol，2013，31(11): 1415-1421. DOI: 10.1200/JCO.2012.46.3299.
[5]
Lui VW, Hedberg ML, Li H, et al. Frequent Mutation of the PI3K Pathway in Head and Neck Cancer Defines Predictive Biomarkers[J]. Cancer Discov，2013，3(7): 761-769DOI: 10.1158/2159-8290.CD-13-0103.
[6]
Iglesias-Bartolome R, Martin D, Gutkind JS. Exploiting the Head and Neck Cancer Oncogenome：Widespread PI3K-mTOR Pathway Alterations and Novel Molecular Targets[J]. Cancer Discov，2013，3(7): 722. DOI: 10.1158/2159-8290.CD-13-0239.
[7]
Pickering CR, Zhang J, Yoo SY, et al. Integrative Genomic Characterization of Oral Squamous Cell Carcinoma Identifies Frequent Somatic Drivers[J]. Cancer Discov，2013，3(7): 770-781. DOI: 10.1158/2159-8290.CD-12-0537.
[8]
史善伟，许宝山. mTORC1/2信号通路在肿瘤治疗中的应用[J/CD].中华口腔医学研究杂志（电子版），2018，12(6): 383-388. DOI: 10.3877/cma.j.issn.1674-1366.2018.06.011.
[9]
Saxton RA, Sabatini DM. mTOR Signaling in Growth，Metabolism，and Disease[J]. Cell，2017，168(6): 960-976. DOI: 10.1016/j.cell.2017.02.004.
[10]
Lien EC, Dibble CC, Toker A. PI3K signaling in cancer：beyond AKT[J]. Curr Opin Cell Biol，2017，45: 62-71. DOI: 10.1016/j.ceb.2017.02.007.
[11]
Mayer IA, Arteaga CL. The PI3K/AKT Pathway as a Target for Cancer Treatment[J]. Annu Rev Med，2016，67: 11-28. DOI: 10.1146/annurev-med-062913-051343.
[12]
Brown JS, Banerji U. Maximising the potential of AKT inhibitors as anti-cancer treatments[J]. Pharmacol Ther，2017，172: 101-115. DOI: 10.1016/j.pharmthera.2016.12.001.
[13]
Yin Y, Hua H, Li M, et al. mTORC2 promotes type I insulin-like growth factor receptor and insulin receptor activation through the tyrosine kinase activity of mTOR[J]. Cell Res，2016，26(1): 46-65. DOI: 10.1038/cr.2015.133.
[14]
Dodd KM, Yang J, Shen MH, et al. mTORC1 drives HIF-1alpha and VEGF-A signalling via multiple mechanisms involving 4E-BP1，S6K1 and STAT3[J]. Oncogene，2015，34(17): 2239-2250. DOI: 10.1038/onc.2014.164.
[15]
Ferris RL, Clump DA, Ohr J, et al. Phase I trial of cetuximab，intensity modulated radiotherapy（IMRT），and ipilimumab in previously untreated，locally advanced head and neck squamous cell carcinoma（PULA HNSCC）[J]. Annals Oncology，2017，28(suppl_5). DOI: 10.1093/annonc/mdx374.014.
[16]
Boeckx C, Op de Beeck K, Wouters A, et al. Overcoming cetuximab resistance in HNSCC：the role of AURKB and DUSP proteins[J]. Cancer Lett，2014，354(2): 365-377. DOI: 10.1016/j.canlet.2014.08.039.
[17]
Kazandjian D, Blumenthal GM, Yuan W, et al. FDA Approval of Gefitinib for the Treatment of Patients with Metastatic EGFR Mutation-Positive Non-Small Cell Lung Cancer[J]. Clin Cancer Res，2016，22(6): 1307-1312. DOI: 10.1158/1078-0432.CCR-15-2266.
[18]
Burotto M, Manasanch EE, Wilkerson J, et al. Gefitinib and erlotinib in metastatic non-small cell lung cancer：a meta-analysis of toxicity and efficacy of randomized clinical trials[J]. Oncologist，2015，20(4): 400-410. DOI: 10.1634/theoncologist.2014-0154.
[19]
Burtness B, Haddad RI, Dinis J, et al. LUX-head and neck 2：Randomized，double-blind，placebo-controlled，phase III trial of afatinib as adjuvant therapy after chemoradiation（CRT）in primary unresected，high/intermediate-risk，squamous cell cancer of the head and neck（HNSCC）patients（pts）[J]. J Clin Oncol，2017，35(15_suppl): 6001. DOI: 10.1200/JCO.2017.35.15_suppl.6001.
[20]
Mok TS, Wu YL, Ahn MJ, et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer[J]. N Engl J Med，2017，376(7): 629-640. DOI: 10.1056/NEJMoa1612674.
[21]
Rosell R, Chaib I, Cai X, et al. Osimertinib and dihydroartemisinin：A novel drug combination targeting head and neck squamous cell carcinoma[J]. J Clin Oncol，2019，37(15_suppl): e17526. DOI: 10.1200/JCO.2019.37.15_suppl.e17526.
[22]
Mathew R. The prognostic role of VEGF in head and neck squamous cell carcinoma[D]. In：Boston University，2017.
[23]
Fury MG, Lee NY, Sherman E, et al. A phase 2 study of bevacizumab with cisplatin plus intensity-modulated radiation therapy for stage III/IVB head and neck squamous cell cancer[J]. Cancer，2012，118(20): 5008-5014. DOI: 10.1002/cncr.27498.
[24]
Seiwert T, Sarantopoulos J, Kallender H, et al. Phase II trial of single-agent foretinib（GSK1363089）in patients with recurrent or metastatic squamous cell carcinoma of the head and neck[J]. Inves New Drugs，2013，31(2): 417-424. DOI: 10.1007/s10637-012-9861-3.
[25]
Dale OT, Aleksic T, Shah KA, et al. IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer[J]. Carcinogenesis，2015，36(6): 648-655. DOI: 10.1093/carcin/bgv053.
[26]
Shin DH, Min HY, El-Naggar AK, et al. Akt/mTOR Counteract the Antitumor Activities of Cixutumumab，an Anti-Insulin-like Growth Factor I Receptor Monoclonal Antibody[J]. Mol Cancer Ther，2011，10(12): 2437-2448. DOI: 10.1158/1535-7163.Mct-11-0235.
[27]
Politz O, Gruenewald S, Jerchel IS, et al. Abstract 4793：Preclinical evaluation of the combination rogaratinib and copanlisib in HNSCC and HCC in preclinical in vitro and in vivo models[J]. Cancer Research，2019，79(13): 4793. DOI: 10.1158/1538-7445.SABCS18-4793.
[28]
Hochhaus A, Larson RA, Guilhot F, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia[J]. N Engl J Med，2017，376(10): 917-927. DOI: 10.1056/NEJMoa1609324.
[29]
Alfieri S, Granata R, Bergamini C, et al. Systemic therapy in metastatic salivary gland carcinomas：A pathology-driven paradigm？[J]. Oral Oncol，2017，66: 58-63. DOI: 10.1016/j.oraloncology.2016.12.016.
[30]
Squarize CH, Castilho RM, Abrahao AC, et al. PTEN deficiency contributes to the development and progression of head and neck cancer[J]. Neoplasia，2013，15(5): 461-471. DOI: 10.1593/neo.121024.
[31]
Mriouah J, Boura C, Pinel S, et al. Cellular response to cetuximab in PTEN-silenced head and neck squamous cell carcinoma cell line[J]. Int J Oncol，2010，37(6): 1555-1563. DOI: 10.3892/ijo_00000809.
[32]
Mayer IA, Abramson VG, Formisano L, et al. A Phase Ib Study of Alpelisib（BYL719），a PI3Kα-Specific Inhibitor，with Letrozole in ER+/HER2- Metastatic Breast Cancer[J]. Clin Cancer Res，2017，23(1): 26-34. DOI: 10.1158/1078-0432.CCR-16-0134.
[33]
Soulieres D, Faivre S, Mesia R, et al. Buparlisib and paclitaxel in patients with platinum-pretreated recurrent or metastatic squamous cell carcinoma of the head and neck（BERIL-1）：a randomised，double-blind，placebo-controlled phase 2 trial[J]. Lancet Oncol，2017，18(3): 323-335. DOI: 10.1016/s1470-2045(17)30064-5.
[34]
Deneka AY，Howard JD，Chung CH. The PI3K Signaling Pathway in Head and Neck Squamous Cell Carcinoma//Burtness B，Golemis EA. Molecular Determinants of Head and Neck Cancer[M]. Second Edition. Berlin：Springer，2018：117-154. DOI：10.1007/978-3-319-78762-6.
[35]
García-Carracedo D, Villaronga MÁ, Álvarez-Teijeiro S, et al. Impact of PI3K/AKT/mTOR pathway activation on the prognosis of patients with head and neck squamous cell carcinomas[J]. Oncotarget，2016，7(20): 29780-29793. DOI: 10.18632/oncotarget.8957.
[36]
Ahmed O, Kuo W-L, Nagilla M, et al. Synergy with combination of AKT inhibitor（MK-2206）and paclitaxel in head and neck squamous cell carcinoma[J]. J Clin Oncology，2013，31(15 suppl): e13532. DOI: 10.1200/jco.2013.31.15_suppl.e13532.
[37]
Schuettler D, Piontek G, Wirth M, et al. Selective inhibition of EGFR downstream signaling reverses the irradiation-enhanced migration of HNSCC cells[J]. Am J Cancer Res，2015，5(9): 2660-2672.
[38]
Sehgal S, Baker H, Vézina C. Rapamycin（AY-22，989），a new antifungal antibiotic[J]. J Antibiot，1975，28(10): 727-732. DOI: 10.7164/antibiotics.28.727.
[39]
Feldman ME, Apsel B, Uotila A, et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2[J]. PLoS Biol，2009，7(2): e1000038. DOI: 10.1371/journal.pbio.1000038.
[40]
Benjamin D, Colombi M, Moroni C, et al. Rapamycin passes the torch：a new generation of mTOR inhibitors[J]. Nat Rev Drug Discov，2011，10(11): 868-880. DOI: 10.1038/nrd3531.
[41]
Rodrik-Outmezguine VS, Okaniwa M, Yao Z, et al. Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor[J]. Nature，2016，534(7606): 272-276. DOI: 10.1038/nature17963.
[42]
Liang X, Deng M, Zhang C, et al. Combined class I histone deacetylase and mTORC1/C2 inhibition suppresses the initiation and recurrence of oral squamous cell carcinomas by repressing SOX2[J]. Cancer Lett，2019，454: 108-119. DOI: 10.1016/j.canlet.2019.04.010.
[43]
Herzog A, Bian Y, Vander Broek R, et al. PI3K/mTOR inhibitor PF-04691502 antitumor activity is enhanced with induction of wild-type TP53 in human xenograft and murine knockout models of head and neck cancer[J]. Clin Cancer Res，2013，19(14): 3808-3819. DOI: 10.1158/1078-0432.CCR-12-2716.
[44]
Cassell A, Freilino ML, Lee J, et al. Targeting TORC1/2 enhances sensitivity to EGFR inhibitors in head and neck cancer preclinical models[J]. Neoplasia，2012，14(11): 1005-1014. DOI: 10.1593/neo.121212.
[45]
中华口腔医学会口腔颌面外科专业委员会肿瘤学组.口腔颌面部恶性肿瘤治疗指南[J].中国口腔颌面外科杂志，2010，8(2): 98-106. DOI: 10.3969/j.issn.1674-1595.2010.07.004.
[46]
王红，吴云腾，郭伟，等. EGFR单抗联合化疗治疗晚期口腔颌面-头颈部鳞状细胞癌近10年临床疗效观察[C]//第十二次全国口腔颌面-头颈肿瘤内科及脉管疾病学术会议暨第二次河南省抗癌协会口腔颌面肿瘤学会会议，郑州，2018.北京：中华口腔医学会，2018：7.
[47]
Mayfield JD, Mercado CE, Kaye FJ, et al. Cetuximab-associated pulmonary toxicity in concurrent chemoradiation for the treatment of a squamous cell carcinoma of the head and neck[J]. Head Neck，2019，41(4): E55-E58. DOI: 10.1002/hed.25528
[48]
Pinto C, Barone CA, Girolomoni G, et al. Management of Skin Reactions During Cetuximab Treatment in Association With Chemotherapy or Radiotherapy：Update of the Italian Expert Recommendations[J]. Am J Clin Oncol，2016，39(4): 407-415. DOI: 10.1097/COC.0000000000000291.
[49]
Lamming DW, Ye L, Katajisto P, et al. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity[J]. Science，2012，335(6076): 1638-1643. DOI: 10.1126/science.1215135.
[50]
Zhang Y, Yan H, Xu Z, et al. Molecular basis for class side effects associated with PI3K/AKT/mTOR pathway inhibitors[J]. Expert Opin Drug Metab Toxicol，2019，15(9): 767-774. DOI: 10.1080/17425255.2019.1663169.
[51]
Zhang XC, Xu C, Mitchell RM, et al. Tumor evolution and intratumor heterogeneity of an oropharyngeal squamous cell carcinoma revealed by whole-genome sequencing[J]. Neoplasia，2013，15(12): 1371-1378. DOI: 10.1593/neo.131400.
[52]
Cellini F, Morganti AG, Genovesi D, et al. Role of microRNA in response to ionizing radiations：evidences and potential impact on clinical practice for radiotherapy[J]. Molecules，2014，19(4): 5379-5401. DOI: 10.3390/molecules19045379.
[53]
Haydar AA, Denton M, West A, et al. Sirolimus-induced pneumonitis：three cases and a review of the literature[J]. Am J Transplant，2004，4(1): 137-139. DOI: 10.1046/j.1600-6135.2003.00292.x
[54]
Wang Z, Valera JC, Zhao X, et al. mTOR co-targeting strategies for head and neck cancer therapy[J]. 2017，36(3): 491-502. DOI: 10.1007/s10555-017-9688-7.
[55]
Pollizzi KN, Powell JD. Regulation of T cells by mTOR：the known knowns and the known unknowns[J]. Trends Immunol，2015，36(1): 13-20. DOI: 10.1016/j.it.2014.11.005.
[56]
Moore EC, Cash HA, Caruso AM, et al. Enhanced Tumor Control with Combination mTOR and PD-L1 Inhibition in Syngeneic Oral Cavity Cancers[J]. Cancer Immunol Res，2016，4(7): 611-620. DOI: 10.1158/2326-6066.CIR-15-0252.
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