TY  - JOUR
A1  - Thomas, Anita
A1  - Slade, Kimberly Sue
A1  - Blaheta, Roman A.
A1  - Markowitsch, Sascha Dennis
A1  - Stenzel, Philipp J.
A1  - Tagscherer, Katrin
A1  - Roth, Wilfried
A1  - Schindeldecker, Mario
A1  - Michaelis, Martin
A1  - Rothweiler, Florian
A1  - Cinatl, Jaroslav
A1  - Dotzauer, Robert Hans
A1  - Vakhrusheva, Olesya
A1  - Albersen, Maarten
A1  - Haferkamp, Axel
A1  - Jüngel, Eva
A1  - Cinatl, Jindrich
A1  - Tsaur, Igor
T1  - Value of c-MET and Associated Signaling Elements for Predicting Outcomes and Targeted Therapy in Penile Cancer
T2  - Cancers
N2  - 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.
KW  - penile cancer
KW  - squamous cell carcinoma
KW  - c-MET
KW  - resistant cell lines
KW  - marker
KW  - targeted therapy
KW  - tivantinib
KW  - cabozantinib
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/83138
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-831386
SN  - 2072-6694
N1  - Funding Information: This research was supported by the Werner Jackstädt-Stiftung-Foundation, Loercher-Foundation for Medical Research, European Urological Scholarship Programme (EUSP), and by the friendly society Hilfe für krebskranke Kinder Frankfurt e.V. and its foundation Frankfurter Stiftung für krebskranke Kinder.
VL  - 14
IS  - 7, art. 1683
SP  - 1
EP  - 15
PB  - MDPI
CY  - Basel
ER  -