Thomas, Anita, Slade, Kimberly Sue, Blaheta, Roman A., Markowitsch, Sascha D., Stenzel, Philipp, Tagscherer, Katrin E., Roth, Wilfried, Schindeldecker, Mario, Michaelis, Martin, Rothweiler, Florian, and others. (2022) Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer. Cancers, 14 (7). Article Number 1683. ISSN 2072-6694. (doi:10.3390/cancers14071683) (KAR id:95208)
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Language: English DOI for this version: 10.3390/cancers14071683
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Official URL: https://doi.org/10.3390/cancers14071683 |
Abstract
Whereas the lack of biomarkers in penile cancer (PeCa) impedes the development of efficacious treatment protocols, preliminary evidence suggests that c-MET and associated signaling elements may be dysregulated in this disorder. In the following study, we investigated whether c-MET and associated key molecular elements may have prognostic and therapeutic utility in PeCa. Formalin-fixed, paraffin-embedded tumor tissue from therapy-naïve patients with invasive PeCa was used for tissue microarray (TMA) analysis. Immunohistochemical staining was performed to determine the expression of the proteins c-MET, PPARg, β-catenin, snail, survivin, and n-MYC. In total, 94 PeCa patients with available tumor tissue were included. The median age was 64.9 years. High-grade tumors were present in 23.4%, and high-risk HPV was detected in 25.5%. The median follow-up was 32.5 months. High expression of snail was associated with HPV-positive tumors. Expression of β-catenin was inversely associated with grading. In both univariate COX regression analysis and the log-rank test, an increased expression of PPARg and c-MET was predictive of inferior disease-specific survival (DSS). Moreover, in multivariate analysis, a higher expression of c-MET was independently associated with worse DSS. Blocking c-MET with cabozantinib and tivantinib induced a significant decrease in viability in the primary PeCa cell line UKF-PeC3 isolated from the tumor tissue as well as in cisplatin- and osimertinib-resistant sublines. Strikingly, a higher sensitivity to tivantinib could be detected in the latter, pointing to the promising option of utilizing this agent in the second-line treatment setting.
Item Type: | Article |
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DOI/Identification number: | 10.3390/cancers14071683 |
Uncontrolled keywords: | penile cancer; squamous cell carcinoma; c-MET; resistant cell lines; marker; targeted therapy; tivantinib; cabozantinib |
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 May 2022 16:15 UTC |
Last Modified: | 30 May 2022 08:37 UTC |
Resource URI: | https://kar.kent.ac.uk/id/eprint/95208 (The current URI for this page, for reference purposes) |
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