Translational Genitourinary Cancer Research

 

Principal Investigators

 

Prof. Lukas Bubendorf

Email | LinkedIn

 

Dr. Clémentine Le Magnen

Email | LinkedIn | ORCID

 

PD Dr. Cyrill Rentsch

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Prof. Dr. med. Hans-Helge Seifert

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Group Members

 

Raphaëlle Servant

Email | LinkedIn | ORCID

 

Michele Garioni

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Dr. Joël Federer-Gsponer

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Dr. David Müller

Email

 

Dr. med. Tatjana Vlajnic

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Our Science

 
 

Being a joint venture between the Institute of Pathology and the Department of Urology at the University Hospital Basel, our laboratory mainly focuses on prostate and bladder cancer translational research. We have assembled a multidisciplinary team of investigators to advance knowledge in the following topics.

 

Cellular and molecular determinants of prostate cancer progression

Prostate cancer (PCa) is the most diagnosed cancer type and a leading cause of cancer-related deaths in men. PCa is often multifocal and can follow various clinical paths from indolent disease causing little/no harm, to aggressive disease, which is not curable. Thus, major clinical needs remain (1) to identify refined prognostic and predictive biomarkers for a better management of the disease and (2) to elucidate mechanisms driving tumor progression and treatment resistance (i.e. castration resistance) in order to improve the outcome of patients with lethal PCa. In this framework, our laboratory aims at gaining a better understanding of factors driving tumor heterogeneity, cancer progression and treatment resistance. Our research primary relies on the use of patient-derived material and involves genomic, phenotypic, and other molecular analyses of longitudinal tumor samples. Using this comprehensive approach, we aim at identifying cellular and molecular factors associated with progression of the disease and to investigate their functional, prognostic, and clinical relevance in PCa. In this context, we particularly focus on studying the contribution of factors associated with stemness and cellular plasticity to tumor progression and castration-resistance. In parallel, our research also involves the development and characterization of clinically relevant models derived from patient material (See Figure). These models represent promising tools to study the development of the disease as well as to dissect mechanisms underlying treatment response and treatment resistance.

Patient-derived organoids. (A) Organoids derived from a patient sample after 15 days in culture (top: low power, bottom: high power). (B) Histological and phenotypic analyses of the patient sample (top panel) and its derived organoid line (bottom panel). Both contain proliferating cells (Ki67+) and exhibit a luminal-like phenotype as demonstrated by expression of the prostate luminal marker NKX3.1 and the absence of expression of the basal marker P63. Scale bar: 20 µm

 

Bladder cancer research

Bladder cancer is the most common cancer of the urinary tract and can be divided in two major groups: non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). NMIBC and MIBC are associated with different clinical outcome, which may be attributed to their distinct molecular signatures. Adjuvant treatment of NMIBC using intravesical Bacillus Calmette-Guérin (BCG) after transurethral resection was introduced more than 40 years ago. While BCG therapy remains the standard of care, critical parameters influencing treatment outcome are still poorly understood. Stemming from these clinical challenges, the research in our laboratory focuses on (1) exploring clonal heterogeneity and tumor evolution and (2) delineating mechanisms underlying resistance to BCG and identifying predictive biomarkers of therapy response.

 

Selected Publications

2018:

Federer-Gsponer, J. R.*, Quintavalle, C.*, Muller, D. C. et al. Delineation of human prostate cancer evolution identifies chromothripsis as a polyclonal event and FKBP4 as a potential driver of castration resistance. J Pathol 245, 74-84 (2018). * Equal contribution

Le Magnen, C., Virk, R. K., Dutta, A. et al. Cooperation of loss of NKX3.1 and inflammation in prostate cancer initiation. Dis Model Mech 11 (2018).

Le Magnen, C., Shen, M. M. & Abate-Shen, C. Lineage Plasticity in Cancer Progression and Treatment. Annu Rev Cancer Biol 2, 271-289 (2018).

Rentsch, C. A., Derre, L., Dugas, S. G. et al. Building on a Solid Foundation: Enhancing Bacillus Calmette-Guerin Therapy. Eur Urol Focus 4, 485-493 (2018).

Navone, N. M., van Weerden, W. M., Vessella, R. L. et al. Movember GAP1 PDX project: An international collection of serially transplantable prostate cancer patient-derived xenograft (PDX) models. Prostate 78, 1262-1282 (2018).

Muller, D. C., Ramo, M., Naegele, K. et al. Donor-derived, metastatic urothelial cancer after kidney transplantation associated with a potentially oncogenic BK polyomavirus. J Pathol 244, 265-270 (2018).

Leighton, X., Bera, A., Eidelman, O. et al. Tissue microarray analysis delineate potential prognostic role of Annexin A7 in prostate cancer progression. PLoS One 13, e0205837 (2018).

Earlier:

 Zou, M., Toivanen, R., Mitrofanova, A. et al. Transdifferentiation as a Mechanism of Treatment Resistance in a Mouse Model of Castration-Resistant Prostate Cancer. Cancer Discov 7, 736-749 (2017).

 Dutta, A.*, Le Magnen, C.*, Mitrofanova, A. et al. Identification of an NKX3.1-G9a-UTY transcriptional regulatory network that controls prostate differentiation. Science 352, 1576-1580 (2016).* Equal contribution

 Le Magnen, C.*, Dutta, A.* & Abate-Shen, C. Optimizing mouse models for precision cancer prevention. Nat Rev Cancer 16, 187-196 (2016). * Equal contribution

Wetterauer, C.*, Vlajnic, T.*, Schuler, J. et al. Early development of human lymphomas in a prostate cancer xenograft program using triple knock-out immunocompromised mice. Prostate 75, 585-592 (2015). * Equal contribution

Rentsch, C. A., Birkhauser, F. D., Biot, C. et al. Bacillus Calmette-Guerin strain differences have an impact on clinical outcome in bladder cancer immunotherapy. Eur Urol 66, 677-688 (2014).

Gsponer, J. R., Braun, M., Scheble, V. J. et al. ERG rearrangement and protein expression in the progression to castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 17, 126-131 (2014).

Le Magnen, C., Bubendorf, L., Rentsch, C. A. et al. Characterization and clinical relevance of ALDHbright populations in prostate cancer. Clin Cancer Res 19, 5361-5371 (2013).

Biot, C., Rentsch, C. A., Gsponer, J. R. et al. Preexisting BCG-specific T cells improve intravesical immunotherapy for bladder cancer. Sci Transl Med 4, 137ra172 (2012).