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

Thomas, Anita, Reetz, Sascha, Stenzel, Philipp, Tagscherer, Katrin, Roth, Wilfried, Schindeldecker, Mario, Michaelis, Martin, Rothweiler, Florian, Cinatl Jr., Jindrich, Cinatl, Jaroslav, and others. (2021) Assessment of PI3K/mTOR/AKT Pathway Elements to Serve as Biomarkers and Therapeutic Targets in Penile Cancer. Cancers, 13 (10). Article Number 2323. E-ISSN 2072-6694. (doi:10.3390/cancers13102323) (KAR id:90384)

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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.

Item Type: Article
DOI/Identification number: 10.3390/cancers13102323
Uncontrolled keywords: penile cancer; AKT; mTOR; cell lines; biomarker; targeted therapy
Subjects: R Medicine > RC Internal medicine > RC254 Neoplasms. Tumors. Oncology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Martin Michaelis
Date Deposited: 27 Sep 2021 18:12 UTC
Last Modified: 14 Nov 2022 23:13 UTC
Resource URI: (The current URI for this page, for reference purposes)
Michaelis, Martin:
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