MP40-09 MOLECULAR ASPECTS OF RESISTANCE TO CISPLATIN AND OSIMERTINIB IN PENILE CANCER

You have accessJournal of UrologyPenile & Testicular Cancer I (MP40)1 Sep 2021MP40-09 MOLECULAR ASPECTS OF RESISTANCE TO CISPLATIN AND OSIMERTINIB IN PENILE CANCER Anita Thomas, Olesya Vakhrusheva, Martin MIchaelis, Jindrich Cinatl, Florian Rothweiler, Maarten Albersen, Axel Haferkamp, Eva Jüngel, and Igor Tsaur ThomasAnita Thomas More articles by this author , VakhrushevaOlesya Vakhrusheva MIchaelisMartin MIchaelis CinatlJindrich Cinatl RothweilerFlorian Rothweiler AlbersenMaarten Albersen HaferkampAxel Haferkamp JüngelEva Jüngel TsaurIgor View All Author Informationhttps://doi.org/10.1097/JU.0000000000002055.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION OBJECTIVE: Metastatic penile cancer (PeCa) is hallmarked rapidly evolving resistance chemotherapy worsening prognosis. Since PeCa a rare disease, translational research aimed at identifying novel options counteracting limited scarcity biomaterials, tumor models as well funding. In the current project, cell lines resistant cisplatin osimertinib were successfully established. Moreover, molecular mechanisms efficacy drug treatment analyzed. METHODS: Therapy-naïve UKF-PeC3 cells adapted growth in presence 2 μg/ml (UKF-PeC3rCIS2) or μM (UKF-PeC3rOSI2). Tumor growth, proliferation, apoptosis, cycle phases regulating proteins akt/mTOR signaling pathway investigated therapy-naïve cisplatin- MTT dye reduction assay, BrdU flow cytometry western blot. Finally, effects with mTOR-inhibitor everolimus on determined both lines. RESULTS: The IC50 (half-maximal effective dose) value for (5.48 vs. 61.76 μg/ml) (5.04 17.02 μM) was increased significantly compared treatment-naïve confirming acquired UKF-PeC3rCIS2 UKF-PeC3rOSI2. Accordingly, showed weaker response viability proliferation assays. Flow detected modulation state resistance. Furthermore, protein expression profiles selected demonstrated an upregulation pAKT, p4EBP1 pmTOR cells. Therapeutic potential further corroborated testing everolimus. CONCLUSIONS: Resistance patterns identified, emphasizing involvement AKT/mTOR paving way development strategies PeCa. Targeting might prolong therapeutic regimens induce re-sensitization treatment-resistant Source Funding: Brigitte- und Dr. Konstanze Wegener-Stiftung © 2021 American Urological Association Education Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e717-e718 Advertisement Copyright Permissions© Inc.MetricsAuthor Information Expand Loading ...