April 2023 - Iris Ertl

Dr. Iris Ertl, PhD

MedUni Wien RESEARCHER OF THE MONTH April 2023

In order to identify novel therapies for bladder cancer, a panel of 23 commercially available cell lines representing a broad spectrum of bladder tumors was used to perform a high-throughput drug screen. Amongst >1700 tested chemical compounds a total of 471 substances exhibited antineoplastic effects. One of these agents, the anti-leukemic drug clofarabine, was studied in more depth. In vitro experiments confirmed potent inhibitory effects of the drug on commercially available and patient-derived cell lines originating from tumours of various disease stages and intrinsic subtypes. To test the effects of clofarabine in vivo, patient-derived cell cultures representing two histologic bladder cancer variants (conventional urothelial carcinoma and sarcomatoid carcinoma) were used to generate mouse xenograft models. Treatment with well-tolerated doses of clofarabine induced massive tumour shrinkage or complete remission in all animals. These findings suggest that clofarabine may represent a highly promising therapeutic option for the clinical management of various subtypes of bladder cancer.

Selected Literature

1. Ertl IE, Lemberger U, Ilijazi D, Hassler MR, Bruchbacher A, Brettner R, et al. Molecular and Pharmacological Bladder Cancer Therapy Screening: Discovery of Clofarabine as a Highly Active Compound. Eur Urol. 2022 Sep;82(3):261-270. doi: 10.1016/j.eururo.2022.03.009.

2. Cornes E, Porta-De-La-Riva M, Aristizábal-Corrales D, Brokate-Llanos AM, García-Rodríguez FJ, Ertl I, et al. Cytoplasmic LSM-1 protein regulates stress responses through the insulin/IGF-1 signaling pathway in Caenorhabditis elegans. RNA. 2015 Sep;21(9):1544-53. doi: 10.1261/rna.052324.115.

3. Ertl I, Porta-De-La-Riva M, Gómez-Orte E, Rubio-Peña K, Corrales D, Cornes E, et al. Functional interplay of two paralogs encoding SWI/SNF chromatin-remodeling accessory subunits during Caenorhabditis elegans development. Genetics. 2016 Mar;202(3):96 1-75. doi: 10.1534/genetics.115.183533.

4. Xu T, Park S, Giaimo BD, Hall D, Ferrante F, Ho DM, Hori K, Ertl I, et al. RBPJ/CBF1 interacts with L3MBTL3/MBT1 to promote repression of Notch signaling via histone demethylase KDM1A/LSD1. EMBO J. 2017 Nov 2;36(21):3232-3249. doi: 10.15252/embj.201796525.

5. Ilijazi D, Pulverer W, Ertl IE, Lemberger U, Kimura S, Abufaraj M, et al. Discovery of Molecular DNA Methylation-Based Biomarkers through Genome-Wide Analysis of Response Patterns to BCG for Bladder Cancer. Cells. 2020 Aug 5;9(8):1839. doi: 10.3390/cells9081839.

6. Trimmel B, Oszwald A, Diemand C, Ertl IE, Lemberger U, Bruchbacher A, et al. Evaluation of APOBEC3 expression as prognostic marker in squamous cell carcinoma of the penis. Sci Rep. 2022 Jul 28;12(1):12911. doi: 10.1038/s41598-022-17056-8.

7. Ertl IE, Brettner R, Kronabitter H, Mohr T, Derdak S, Jeitler M, et al. The SMARCD Family of SWI/SNF Accessory Proteins Is Involved in the Transcriptional Regulation of Androgen Receptor-Driven Genes and Plays a Role in Various Essential Processes of Prostate Cancer. Cells. 2022 Dec 28;12(1):124. doi: 10.3390/cells12010124.