• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

评估PI3K/mTOR/AKT信号通路元件作为阴茎癌生物标志物和治疗靶点的作用

Assessment of PI3K/mTOR/AKT Pathway Elements to Serve as Biomarkers and Therapeutic Targets in Penile Cancer.

作者信息

Thomas Anita, Reetz Sascha, Stenzel Philipp, Tagscherer Katrin, Roth Wilfried, Schindeldecker Mario, Michaelis Martin, Rothweiler Florian, Cinatl Jindrich, Cinatl Jaroslav, Dotzauer Robert, Vakhrusheva Olesya, Albersen Maarten, Macher-Goeppinger Stephan, Haferkamp Axel, Juengel Eva, Neisius Andreas, Tsaur Igor

机构信息

Department of Urology and Pediatric Urology, University Medicine Mainz, 55122 Mainz, Germany.

Department of Pathology, University Medicine Mainz, 55122 Mainz, Germany.

出版信息

Cancers (Basel). 2021 May 12;13(10):2323. doi: 10.3390/cancers13102323.

DOI:10.3390/cancers13102323
PMID:34066040
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8151654/
Abstract

The PI3K/mTOR/AKT pathway might represent an intriguing option for treatment of penile cancer (PeCa). We aimed to assess whether members of this pathway might serve as biomarkers and targets for systemic therapy. Tissue of primary cancer from treatment-naïve PeCa patients was used for tissue microarray analysis. Immunohistochemical staining was performed with antibodies against AKT, pAKT, mTOR, pmTOR, pS6, pPRAS, p4EBP1, S6K1 and pp70S6K. Protein expression was correlated with clinicopathological characteristics as well as overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and metastasis-free survival (MFS). AKT inhibition was tested in two primarily established, treatment-naïve PeCa cell lines by treatment with capivasertib and analysis of cell viability and chemotaxis. A total of 76 patients surgically treated for invasive PeCa were included. Higher expression of AKT was significantly more prevalent in high-grade tumors and predictive of DSS and OS in the Kaplan-Meier analysis, and an independent predictor of worse OS and DSS in the multivariate regression analysis. Treatment with pan-AKT inhibitor capivasertib in PeCa cell lines induced a significant downregulation of both total AKT and pAKT as well as decreased cell viability and chemotaxis. Selected protein candidates of the mTOR/AKT signaling pathway demonstrate association with histological and survival parameters of PeCa patients, whereas AKT appears to be the most promising one.

摘要

PI3K/mTOR/AKT信号通路可能是阴茎癌（PeCa）治疗中一个引人关注的选择。我们旨在评估该信号通路的成员是否可作为生物标志物和全身治疗的靶点。从未接受过治疗的PeCa患者的原发性癌组织用于组织芯片分析。使用抗AKT、pAKT、mTOR、pmTOR、pS6、pPRAS、p4EBP1、S6K1和pp70S6K的抗体进行免疫组织化学染色。蛋白表达与临床病理特征以及总生存期（OS）、疾病特异性生存期（DSS）、无复发生存期（RFS）和无转移生存期（MFS）相关。通过用卡匹西利治疗并分析细胞活力和趋化性，在两种主要建立的、未接受过治疗的PeCa细胞系中测试了AKT抑制作用。总共纳入了76例接受手术治疗的浸润性PeCa患者。在高级别肿瘤中，AKT的高表达明显更为普遍，在Kaplan-Meier分析中可预测DSS和OS，在多变量回归分析中是OS和DSS较差的独立预测因素。在PeCa细胞系中用泛AKT抑制剂卡匹西利治疗可显著下调总AKT和pAKT，并降低细胞活力和趋化性。mTOR/AKT信号通路的选定蛋白候选物显示与PeCa患者的组织学和生存参数相关，而AKT似乎是最有前景的一个。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f0/8151654/c076f8203747/cancers-13-02323-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f0/8151654/aa4405a8ce28/cancers-13-02323-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f0/8151654/7e8d3ff8965c/cancers-13-02323-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f0/8151654/272358097e49/cancers-13-02323-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f0/8151654/4e3c5008b649/cancers-13-02323-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f0/8151654/c076f8203747/cancers-13-02323-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f0/8151654/aa4405a8ce28/cancers-13-02323-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f0/8151654/7e8d3ff8965c/cancers-13-02323-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f0/8151654/272358097e49/cancers-13-02323-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f0/8151654/4e3c5008b649/cancers-13-02323-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f0/8151654/c076f8203747/cancers-13-02323-g005.jpg

相似文献

1
Assessment of PI3K/mTOR/AKT Pathway Elements to Serve as Biomarkers and Therapeutic Targets in Penile Cancer.评估PI3K/mTOR/AKT信号通路元件作为阴茎癌生物标志物和治疗靶点的作用
Cancers (Basel). 2021 May 12;13(10):2323. doi: 10.3390/cancers13102323.
2
Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer.c-MET及相关信号元件在预测阴茎癌预后和靶向治疗中的价值
Cancers (Basel). 2022 Mar 25;14(7):1683. doi: 10.3390/cancers14071683.
3
Impact of PI3K-AKT-mTOR Signaling Pathway Up-regulation on Prognosis of Penile Squamous-Cell Carcinoma: Results From a Tissue Microarray Study and Review of the Literature.PI3K-AKT-mTOR 信号通路上调对阴茎鳞癌预后的影响：组织微阵列研究及文献复习的结果。
Clin Genitourin Cancer. 2019 Feb;17(1):e80-e91. doi: 10.1016/j.clgc.2018.09.012. Epub 2018 Sep 22.
4
Analysis of PI3K/mTOR Pathway Biomarkers and Their Prognostic Value in Women with Hormone Receptor-Positive, HER2-Negative Early Breast Cancer.分析激素受体阳性、HER2 阴性早期乳腺癌中 PI3K/mTOR 通路生物标志物及其预后价值。
Transl Oncol. 2016 Apr;9(2):114-123. doi: 10.1016/j.tranon.2016.01.001.
5
Abnormal Protein Glycosylation and Activated PI3K/Akt/mTOR Pathway: Role in Bladder Cancer Prognosis and Targeted Therapeutics.异常蛋白质糖基化与激活的PI3K/Akt/mTOR信号通路：在膀胱癌预后及靶向治疗中的作用
PLoS One. 2015 Nov 16;10(11):e0141253. doi: 10.1371/journal.pone.0141253. eCollection 2015.
6
Prognostic relevance of the mTOR pathway in renal cell carcinoma: implications for molecular patient selection for targeted therapy.mTOR通路在肾细胞癌中的预后相关性：对分子靶向治疗患者选择的意义
Cancer. 2007 Jun 1;109(11):2257-67. doi: 10.1002/cncr.22677.
7
PI3K-AKT-mTOR pathway proteins are differently expressed in oral carcinogenesis.PI3K-AKT-mTOR信号通路蛋白在口腔癌发生过程中表达各异。
J Oral Pathol Med. 2016 Nov;45(10):746-752. doi: 10.1111/jop.12440. Epub 2016 Mar 15.
8
mTOR signaling pathway in penile squamous cell carcinoma: pmTOR and peIF4E over expression correlate with aggressive tumor behavior.阴茎鳞状细胞癌中的 mTOR 信号通路：pmTOR 和 peIF4E 的过度表达与侵袭性肿瘤行为相关。
J Urol. 2013 Dec;190(6):2288-95. doi: 10.1016/j.juro.2013.06.015. Epub 2013 Jun 11.
9
Predictive value of EGFR-PI3K-pAKT-mTOR-pS6 pathway in sinonasal squamous cell carcinomas.EGFR-PI3K-pAKT-mTOR-pS6信号通路在鼻窦鳞状细胞癌中的预测价值
Acta Otorrinolaringol Esp (Engl Ed). 2019 Jan-Feb;70(1):16-24. doi: 10.1016/j.otorri.2017.10.005. Epub 2018 Mar 21.
10
Penile Cancer-Derived Cells Molecularly Characterized as Models to Guide Targeted Therapies.阴茎癌源性细胞的分子特征可作为指导靶向治疗的模型。
Cells. 2021 Apr 6;10(4):814. doi: 10.3390/cells10040814.

引用本文的文献

1
Tumor-infiltrating plasma cells are a prognostic factor in penile squamous cell carcinoma.肿瘤浸润浆细胞是阴茎鳞状细胞癌的一个预后因素。
Virchows Arch. 2025 Jan 14. doi: 10.1007/s00428-024-04013-1.
2
Identification of new tissue markers for the monitoring and standardization of penile cancer according to the degree of differentiation.根据分化程度鉴定用于阴茎癌监测和标准化的新组织标志物。
Histol Histopathol. 2025 Jul;40(7):1013-1039. doi: 10.14670/HH-18-846. Epub 2024 Nov 7.
3
Experimental and Clinical Advances in Counteracting Progression of Solid Cancers.

本文引用的文献

1
Systemic treatment of penile squamous cell carcinoma-hurdles and hopes of preclinical models and clinical regimens: a narrative review.阴茎鳞状细胞癌的全身治疗——临床前模型和临床治疗方案的障碍与希望：一项叙述性综述
Transl Androl Urol. 2021 Oct;10(10):4085-4098. doi: 10.21037/tau-20-945.
2
Penile cancer.阴茎癌
Nat Rev Dis Primers. 2021 Feb 11;7(1):11. doi: 10.1038/s41572-021-00246-5.
3
The Role of mTOR Signaling as a Therapeutic Target in Cancer.mTOR 信号在癌症治疗中的作用。
对抗实体癌进展的实验与临床进展
Cancers (Basel). 2023 Mar 24;15(7):1956. doi: 10.3390/cancers15071956.
4
Increased HRD score in cisplatin resistant penile cancer cells.顺铂耐药性阴茎癌细胞中 HRD 评分增加。
BMC Cancer. 2022 Dec 23;22(1):1352. doi: 10.1186/s12885-022-10432-7.
5
Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer.c-MET及相关信号元件在预测阴茎癌预后和靶向治疗中的价值
Cancers (Basel). 2022 Mar 25;14(7):1683. doi: 10.3390/cancers14071683.
Int J Mol Sci. 2021 Feb 9;22(4):1743. doi: 10.3390/ijms22041743.
4
Effect of Capivasertib in Patients With an AKT1 E17K-Mutated Tumor: NCI-MATCH Subprotocol EAY131-Y Nonrandomized Trial.AKT1 E17K 突变肿瘤患者中 Capivasertib 的疗效：NCI-MATCH 子方案 EAY131-Y 非随机试验。
JAMA Oncol. 2021 Feb 1;7(2):271-278. doi: 10.1001/jamaoncol.2020.6741.
5
A phase I dose-escalation study of enzalutamide in combination with the AKT inhibitor AZD5363 (capivasertib) in patients with metastatic castration-resistant prostate cancer.一项评估恩扎卢胺联合 AKT 抑制剂 AZD5363（capivasertib）治疗转移性去势抵抗性前列腺癌患者的 I 期剂量递增研究。
Ann Oncol. 2020 May;31(5):619-625. doi: 10.1016/j.annonc.2020.01.074. Epub 2020 Feb 21.
6
Comparing PI3K/Akt Inhibitors Used in Ovarian Cancer Treatment.比较用于卵巢癌治疗的PI3K/Akt抑制剂
Front Pharmacol. 2020 Mar 3;11:206. doi: 10.3389/fphar.2020.00206. eCollection 2020.
7
Overexpression of p-Akt, p-mTOR and p-eIF4E proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer.p-Akt、p-mTOR 和 p-eIF4E 蛋白的过表达与非小细胞肺癌的转移和不良预后相关。
PLoS One. 2020 Feb 5;15(2):e0227768. doi: 10.1371/journal.pone.0227768. eCollection 2020.
8
Capivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial.卡培他滨联合紫杉醇对比安慰剂联合紫杉醇作为转移性三阴性乳腺癌一线治疗：PAKT 试验。
J Clin Oncol. 2020 Feb 10;38(5):423-433. doi: 10.1200/JCO.19.00368. Epub 2019 Dec 16.
9
Proliferation and AKT Activity Biomarker Analyses after Capivasertib (AZD5363) Treatment of Patients with ER Invasive Breast Cancer (STAKT).卡培他滨（AZD5363）治疗 ER 浸润性乳腺癌（STAKT）患者后的增殖和 AKT 活性生物标志物分析。
Clin Cancer Res. 2020 Apr 1;26(7):1574-1585. doi: 10.1158/1078-0432.CCR-19-3053. Epub 2019 Dec 13.
10
PI3K/Akt/mTOR inhibitors in cancer: At the bench and bedside.PI3K/Akt/mTOR 抑制剂在癌症中的应用：从实验室到临床。
Semin Cancer Biol. 2019 Dec;59:125-132. doi: 10.1016/j.semcancer.2019.07.009. Epub 2019 Jul 16.