PI3K/AKT/mTOR信号通路在腺样囊性癌中的研究进展

doi:10.13591/j.cnki.kqyx.2026.07.010

摘要/Abstract

摘要：

腺样囊性癌(adenoid cystic carcinoma,ACC)是口腔颌面外科常见的恶性肿瘤之一,具有侵袭性强、易复发和远处转移的特点,临床治疗面临巨大挑战。PI3K/AKT/mTOR通路是细胞内重要的信号转导通路,参与调控细胞增殖、存活、代谢和迁移等多种生物学过程。研究表明,ACC中常存在PI3K/AKT/mTOR通路的异常激活,这种激活不仅促进了肿瘤细胞的增殖和侵袭,还与其耐药性和不良预后密切相关。此外,针对PI3K/AKT/mTOR通路的靶向治疗在ACC的临床前研究中显示出潜在疗效,为改善患者预后提供了新思路。本文综述了PI3K/AKT/mTOR信号通路在ACC中的调控机制、生物学功能及与其他信号通路的交互作用的研究进展,旨在为未来深入了解ACC发病机制和新药物、新治疗方法的开发提供启示及参考。

关键词: 腺样囊性癌, 唾液腺, PI3K/AKT/mTOR, 信号通路

Abstract:

Adenoid cystic carcinoma(ACC)is a common malignant tumor encountered in oral and maxillofacial surgery, characterized by its aggressive nature, frequent recurrence, and distant metastasis, posing significant challenges in clinical treatment. The PI3K/AKT/mTOR pathway stands as a crucial intracellular signaling cascade, involved in regulating various biological processes such as cell proliferation, survival, metabolism, and migration. Studies have revealed the abnormal activation of the PI3K/AKT/mTOR pathway in ACC, which not only promotes tumor cell proliferation and invasion but also closely correlates with drug resistance and poor prognosis. Furthermore, targeted therapies against the PI3K/AKT/mTOR pathway have demonstrated potential efficacy in preclinical studies on ACC, offering new avenues for improving patient outcomes. This article provides a comprehensive review of the regulatory mechanisms, biological functions, and interactions with other signaling pathways of the PI3K/AKT/mTOR signaling cascade in ACC. It aims to offer insights and references for future in-depth understanding of ACC pathophysiology and the development of novel drugs and therapeutic approaches.

Key words: adenoid cystic carcinoma, salivary gland, PI3K/AKT/mTOR, signaling pathway

中图分类号:

R739.87

陈钰, 陈文革. PI3K/AKT/mTOR信号通路在腺样囊性癌中的研究进展[J]. 口腔医学, 2026, 46(7): 549-554.

CHEN Yu, CHEN Wenge. Research progress of PI3K/AKT/mTOR signaling pathway in adenoid cystic carcinoma[J]. Stomatology, 2026, 46(7): 549-554.

参考文献 41

[1]	de Morais EF, da Silva LP, Moreira DGL, et al. Prognostic factors and survival in adenoid cystic carcinoma of the head and neck: A retrospective clinical and histopathological analysis of patients seen at a cancer center[J]. Head Neck Pathol, 2021, 15(2): 416-424. doi: 10.1007/s12105-020-01210-7
[2]	Gillard DM, Farzal Z, Ryan WR. Update on thetreatment of salivary gland carcinomas[J]. Surg Oncol Clin N Am, 2024, 33(4): 747-760. doi: 10.1016/j.soc.2024.04.008
[3]	Skálová A, Klubíčková N, Bradová M, et al. Discovery of novel TULP4/ACTN4/EWSR1/ACTB ::MYB and ESRRG:: DNM3 fusions expands molecular landscape of adenoid cystic carcinoma beyond fusions between MYB/MYBL1 and NFIB genes[J]. Am J Surg Pathol, 2024, 48(12): 1503-1511. doi: 10.1097/PAS.0000000000002304 pmid: 39235305
[4]	Nuzzolese I, Bonomo P, Orlandi E, et al. Editorial: Diagnosis, epidemiology and treatment of salivary gland carcinomas[J]. Front Oncol, 2024, 14: 1379584. doi: 10.3389/fonc.2024.1379584
[5]	Sawant PR, Dhume MMS, Spadigam A, et al. Submandibular and sublingual salivary gland involvement in adenoid cystic carcinoma[J]. Autops Case Rep, 2024, 14: e2024500.
[6]	Sonone AM, Hande A, Patil SK, et al. Unusual presentation of adenoid cystic carcinoma of the tongue: A case report and review of the literature[J]. Cureus, 2024, 16(5): e60825.
[7]	Nair S, Bavaskar M, Pt A, et al. Surgical management of patients with distant metastasized adenoid cystic carcinoma of the head and neck[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2024, 138(3): 362-366. doi: 10.1016/j.oooo.2024.05.004
[8]	Zhu YL, Li L, Wang S, et al. Molecular mapping in head and neck adenoid cystic carcinoma by pathological grade using whole-exome sequencing and spatial transcriptome[J]. Hum Pathol, 2025, 157: 105758. doi: 10.1016/j.humpath.2025.105758
[9]	He Y, Sun MM, Zhang GG, et al. Targeting PI3K/Akt signal transduction for cancer therapy[J]. Signal Transduct Target Ther, 2021, 6(1): 425.
[10]	Huang XQ, You L, Nepovimova E, et al. Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK)[J]. J Enzyme Inhib Med Chem, 2023, 38(1): 2237209. doi: 10.1080/14756366.2023.2237209
[11]	Masatoshi N, Ko F. Adipocyte-conditioned medium induces tamoxifen resistance by activating PI3K/Akt/mTOR pathway in estrogen receptor-positive breast cancer cells[J]. Biochim Biophys Acta Mol Cell Res, 2024, 1871(7): 119821. doi: 10.1016/j.bbamcr.2024.119821
[12]	康小红, 王珂, 王颖, 等. 赖氨酸羟化酶2诱导肺癌HCC827细胞对奥希替尼耐药的机制研究[J]. 中华肿瘤杂志, 2020, 42(3):210-215.
[13]	周静, 王春友, 刘涛, 等. PI3K/mTOR信号通路参与胰腺肿瘤干细胞样SP细胞生存增殖的调控[J]. 中华医学杂志, 2008, 88(42):2994-2998.
[14]	Boutouja F, Stiehm CM, Platta HW. mTOR: A cellular regulator interface in health and disease[J]. Cells, 2019, 8(1): 18. doi: 10.3390/cells8010018
[15]	Yang YX, Chen D, Liu H, et al. Increased expression of lncRNA CASC9 promotes tumor progression by suppressing autophagy-mediated cell apoptosis via the AKT/mTOR pathway in oral squamous cell carcinoma[J]. Cell Death Dis, 2019, 10(2): 41. doi: 10.1038/s41419-018-1280-8
[16]	Hou CX, Wang L, Cai M, et al. Sphk1 promotes salivary adenoid cystic carcinoma progression via PI3K/Akt signaling[J]. Pathol Res Pract, 2021, 227: 153620. doi: 10.1016/j.prp.2021.153620
[17]	Chai SL, Wen ZH, Zhang RX, et al. CCL25/CCR9 interaction promotes the malignant behavior of salivary adenoid cystic carcinoma via the PI3K/AKT signaling pathway[J]. Peer J, 2022, 10: e13844.
[18]	Ren YX, Hong YL, He WT, et al. EGF/EGFR promotes salivary adenoid cystic carcinoma cell malignant neural invasion via activation of PI3K/AKT and MEK/ERK signaling[J]. Curr Cancer Drug Targets, 2022, 22(7): 603-616. doi: 10.2174/1568009622666220411112312
[19]	Liu XN, Zhang WC, Guo H, et al. miR-98 functions as a tumor suppressor in salivary adenoid cystic carcinomas[J]. Onco Targets Ther, 2016, 9: 1777-1786.
[20]	Tokat ÜM, Adibi A, Aydın E, et al. Personalized immunotherapy achieves complete response in metastatic adenoid cystic carcinoma despite lack of conventional biomarkers[J]. Curr Oncol, 2024, 31(10): 5838-5849. doi: 10.3390/curroncol31100434 pmid: 39451738
[21]	de Carvalho Kimura T, de Lima-Souza RA, Maciel TF, et al. Dynamic role of miRNAs in salivary gland carcinomas: From biomarkers to therapeutic targets[J]. Head Neck Pathol, 2024, 18(1): 12. doi: 10.1007/s12105-023-01603-4 pmid: 38393615
[22]	Tang YT, Zhu QH, Yang L, et al. miR-200b-5p inhibits tumor progression in salivary adenoid cystic carcinoma via targeting BTBD1[J]. Cell Signal, 2023, 109: 110748. doi: 10.1016/j.cellsig.2023.110748
[23]	Han NN, Li X, Wang YP, et al. HIF-1α induced NID1 expression promotes pulmonary metastases via the PI3K-AKT pathway in salivary gland adenoid cystic carcinoma[J]. Oral Oncol, 2022, 131: 105940. doi: 10.1016/j.oraloncology.2022.105940
[24]	Xu ZD, Hao T, Gan YH. RhoG/Rac1 signaling pathway involved in migration and invasion of salivary adenoid cystic carcinoma cells[J]. Oral Dis, 2020, 26(2): 302-312. doi: 10.1111/odi.v26.2
[25]	Li X, Jiang X, Gao F, et al. Study and evaluation of a gelatin- silver oxide nanoparticles releasing nitric oxide production of wound healing dressing for diabetic ulcer[J]. PLoS One, 2024, 19(6): e0298124. doi: 10.1371/journal.pone.0298124
[26]	Liu CF, He LH, Wang JX, et al. Anti-angiogenic effect of Shikonin in rheumatoid arthritis by downregulating PI3K/AKT and MAPKs signaling pathways[J]. J Ethnopharmacol, 2020, 260: 113039. doi: 10.1016/j.jep.2020.113039
[27]	Zeng Z, Huang WD, Gao Q, et al. Retracted/Arnebin-1 promotes angiogenesis by inducing ENOS, VEGF and HIF-1α expression through the PI3K-dependent pathway[J]. Int J Mol Med, 2023, 51(5): 38. doi: 10.3892/ijmm
[28]	Michaelides I, Künzel J, Ettl T, et al. Adenoid cystic carcinoma of the salivary glands: A pilot study of potential therapeutic targets and characterization of the immunological tumor environment and angiogenesis[J]. Eur Arch Otorhinolaryngol, 2023, 280(6): 2937-2944. doi: 10.1007/s00405-023-07884-3 pmid: 36856809
[29]	马佳睿, 徐芳芷, 左惠演, 等. PI3K/AKT通过激活糖酵解促进巨噬细胞M1极化[J]. 中国心血管杂志, 2023, 28(2): 145-151.
[30]	Xu ZY, Han J, Yang K, et al. HSP27 promotes vasculogenic mimicry formation in human salivary adenoid cystic carcinomavia the AKT-MMP-2/9 pathway[J]. Oral Surg Oral Med Oral Pathol Oral Radiol, 2024, 137(5): 515-528. doi: 10.1016/j.oooo.2024.02.016
[31]	刘玉霞, 郑心, 梁冉冉, 等. 黄芪甲苷基于ILT4-PI3K/Akt-B7-H3通路对NSCLC免疫逃逸机制影响的实验研究[J]. 中药材, 2021, 44(11): 2677-2682.
[32]	杨心怡, 黄薇薇, 黄丽, 等. CENPF调控PI3K/AKT信号通路影响唾液腺腺样囊性癌进展[J]. 口腔医学研究, 2024, 40(9): 803-809. doi: 10.13701/j.cnki.kqyxyj.2024.09.009
[33]	Cui YJ, Zhang Y, Liu YP, et al. EN1 promotes lung metastasis of salivary adenoid cystic carcinoma by regulating the PI3K-AKT pathway and epithelial-mesenchymal transition[J]. Cancer Cell Int, 2024, 24(1): 51. doi: 10.1186/s12935-024-03230-7 pmid: 38291456
[34]	Yang Z, Liu XP, Zhu J, et al. Inhibiting intracellular CD28 in cancer cells enhances antitumor immunity and overcomes anti-PD-1 resistance via targeting PD-L1[J]. Cancer Cell, 2025, 43(1): 86-102.e10. doi: 10.1016/j.ccell.2024.11.008
[35]	Miricescu D, Totan A, Stanescu-SpinuII, et al. PI3K/AKT/mTOR signaling pathway in breast cancer: From molecular landscape to clinical aspects[J]. Int J Mol Sci, 2020, 22(1): 173. doi: 10.3390/ijms22010173
[36]	柴国超, 张素欣. 涎腺导管癌PI3K/AKT/mTOR信号通路中高频突变基因的研究进展[J]. 国际口腔医学杂志, 2021, 48(6): 731-736.
[37]	欧阳黛峤, 廖贵清. 唾液腺腺样囊性癌中PI3K/Akt/mTOR信号通路活化水平及其临床意义[C]// 第十四次中国口腔颌面外科学术会议论文汇编. 重庆, 2018: 510.
[38]	Fu QY, Liu XC, Xia HF, et al. Interferon-γ induces immunosuppression in salivary adenoid cystic carcinoma by regulating programmed death ligand 1 secretion[J]. Int J Oral Sci, 2022, 14(1): 47. doi: 10.1038/s41368-022-00197-x
[39]	Wang Y, Hu JZ, Wang YA, et al. EGFR activation induced Snail-dependent EMT and myc-dependent PD-L1 in human salivary adenoid cystic carcinoma cells[J]. Cell Cycle, 2018, 17(12): 1457-1470. doi: 10.1080/15384101.2018.1489177 pmid: 29954240
[40]	FDA. FDA approves inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast cancer[OB/OL]. (2024-10-10)[2025-09-20]. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-inavolisib-palbociclib-and-fulvestrant-endocrine-resistant-pik3ca-mutated-hr-positive.
[41]	Hillmann P, Fabbro D. PI3K/mTOR pathway inhibition: Opportunities in oncology and rare genetic diseases[J]. Int J Mol Sci, 2019, 20(22): 5792. doi: 10.3390/ijms20225792