TY  - JOUR
A1  - Krebs, Markus
A1  - Solimando, Antonio Giovanni
A1  - Kalogirou, Charis
A1  - Marquardt, André
A1  - Frank, Torsten
A1  - Sokolakis, Ioannis
A1  - Hatzichristodoulou, Georgios
A1  - Kneitz, Susanne
A1  - Bargou, Ralf
A1  - Kübler, Hubert
A1  - Schilling, Bastian
A1  - Spahn, Martin
A1  - Kneitz, Burkhard
T1  - miR-221-3p Regulates VEGFR2 Expression in High-Risk Prostate Cancer and Represents an Escape Mechanism from Sunitinib In Vitro
JF  - Journal of Clinical Medicine
N2  - Downregulation of miR-221-3p expression in prostate cancer (PCa) predicted overall and cancer-specific survival of high-risk PCa patients. Apart from PCa, miR-221-3p expression levels predicted a response to tyrosine kinase inhibitors (TKI) in clear cell renal cell carcinoma (ccRCC) patients. Since this role of miR-221-3p was explained with a specific targeting of VEGFR2, we examined whether miR-221-3p regulated VEGFR2 in PCa. First, we confirmed VEGFR2/KDR as a target gene of miR-221-3p in PCa cells by applying Luciferase reporter assays and Western blotting experiments. Although VEGFR2 was mainly downregulated in the PCa cohort of the TCGA (The Cancer Genome Atlas) database, VEGFR2 was upregulated in our high-risk PCa cohort (n = 142) and predicted clinical progression. In vitro miR-221-3p acted as an escape mechanism from TKI in PC3 cells, as displayed by proliferation and apoptosis assays. Moreover, we confirmed that Sunitinib induced an interferon-related gene signature in PC3 cells by analyzing external microarray data and by demonstrating a significant upregulation of miR-221-3p/miR-222-3p after Sunitinib exposure. Our findings bear a clinical perspective for high-risk PCa patients with low miR-221-3p levels since this could predict a favorable TKI response. Apart from this therapeutic niche, we identified a partially oncogenic function of miR-221-3p as an escape mechanism from VEGFR2 inhibition.
KW  - microRNA-221
KW  - high-risk Prostate Cancer
KW  - angiogenesis
KW  - Sunitinib
KW  - Tyrosine kinase inhibition
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203168
SN  - 2077-0383
VL  - 9
IS  - 3
ER  - 
TY  - JOUR
A1  - Argentiero, Antonella
A1  - Solimando, Antonio Giovanni
A1  - Krebs, Markus
A1  - Leone, Patrizia
A1  - Susca, Nicola
A1  - Brunetti, Oronzo
A1  - Racanelli, Vito
A1  - Vacca, Angelo
A1  - Silvestris, Nicola
T1  - Anti-angiogenesis and immunotherapy: novel paradigms to envision tailored approaches in renal cell-carcinoma
JF  - Journal of Clinical Medicine
N2  - Although decision making strategy based on clinico-histopathological criteria is well established, renal cell carcinoma (RCC) represents a spectrum of biological ecosystems characterized by distinct genetic and molecular alterations, diverse clinical courses and potential specific therapeutic vulnerabilities. Given the plethora of drugs available, the subtype-tailored treatment to RCC subtype holds the potential to improve patient outcome, shrinking treatment-related morbidity and cost. The emerging knowledge of the molecular taxonomy of RCC is evolving, whilst the antiangiogenic and immunotherapy landscape maintains and reinforces their potential. Although several prognostic factors of survival in patients with RCC have been described, no reliable predictive biomarkers of treatment individual sensitivity or resistance have been identified. In this review, we summarize the available evidence able to prompt more precise and individualized patient selection in well-designed clinical trials, covering the unmet need of medical choices in the era of next-generation anti-angiogenesis and immunotherapy.
KW  - renal cell carcinoma
KW  - angiogenesis
KW  - immune-checkpoint inhibitor
KW  - tumor microenvironment
KW  - molecular subtypes
KW  - prognostic-biomarkers
KW  - predictive factors
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-205846
SN  - 2077-0383
VL  - 9
IS  - 5
ER  -