NCT Research

CCRP Urogenital

Summary

Clinical and translational research activities focus on development of personalized therapies, search for prognostic and predictive biomarkers.

CCRP Urogenital
 

Member designated as Contact Person

PD Dr. Grüllich
Medical Oncology

 
 
 

Prof. Dr. Stefan Duensing
Molecular Urology, Heidelberg University Hospital

PD Dr. Carsten Grüllich
Dept. of Medical Oncology, NCT/Heidelberg University Hospital

Prof. Dr. Markus Hohenfellner
Dept. of Urology, Heidelberg University Hospital

Prof. Dr. Dirk Jäger

Dept. of Medical Oncology, NCT/Heidelberg University Hospital   

Prof. Dr. Holger Sültmann

Division of Cancer Genome Research, German Cancer Research Center

  1. S. Zschäbitz, F. Lasitschka, D. Jäger, C. Grüllich. Activity of immune checkpoint inhibition in platinum refractory germ cell tumors. Annals of Oncology (2016) 27 (7): 1356-1360
  2. Rouven Höfflin, Bernd Lahrmann, Gregor Warsow, Daniel Hübschmann, Cathleen Spath, Britta Walter, Xin Chen, Luisa Hofer, Stephan Macher-Goeppinger, Yanis Tolstov, Nina Korzeniewski, Anette Duensing, Carsten Grüllich, Dirk Jäger, Sven Perner, Gita Schönberg, Sanjay Isaac, Joanne Nyarangi-Dix, Gencay Hatiboglu, Dogu Teber, Boris Hadaschik, Sascha Pahernik, Wilfried Roth, Roland Eils, Matthias Schlessner, Holger Sültmann, Markus Hohenfellner, Niels Grabe, and Stefan Duensing. Spatial niche formation but not malignant progression is a driving force for intratumoral heterogeneity. Nature Communications, 13 Jun 2016 DOI: 10.1038/ncomms11845
  3. Stefanie Zschäbitz, Sonia Vallet, Boris Hadaschik, Daniel Debatin, Stefan Fuxius, Andreas Karcher, Sascha Pahernik, Cathleen Spath, Stefan Duensing, Dirk Jäger, Markus Hohenfellner, Carsten Grüllich. Efficacy of Cabazitaxel Treatment in Metastatic Castration Resistant Prostate Cancer in Second and Later Lines. An Experience from Two German Centers. Journal of cancer 2017; 8(4):  507-51 2. doi: 10.7150/jca.17644
  4. Stefanie Zschäbitz, Felix Lasitschk, Boris Hadaschik, Ralf-Dieter Hofheinz, , Kathleen Jentsch-Ullrich, Marcus Grüner, Dirk Jäger, Carsten Grüllich. Response to anti-programmed cell death protein-1 antibodies in men treated for platinum refractory germ cell cancer relapsed after high-dose chemotherapy and stem cell transplantation. European Journal of Cancer. Volume 76, May 2017, Pages 1–7
  5. Steffen Dietz,* Holger Sültmann*, YueJun Du, Eva Reisinger, Anja Lisa Riediger, Anna-Lena Volckmar, Albrecht Stenzinger, Matthias Schlesner, Dirk Jäger, Markus Hohenfellner, Stefan Duensing, Carsten Grüllich# and Sascha Pahernik#, Patient-specific  molecular  alterations  are  associated  with metastatic clear cell renal cell cancer progressing under tyrosine kinase inhibitor therapy. # shared senior author Oncotarget May 23, 2017
  6. Peter J Goebell, Christian Doehn, Carsten Grüllich, Viktor Grünwald, Thomas Steiner, Rainer Ehneß, Manfred Welslau. The PAZOREAL noninterventional study to assess effectiveness and safety of pazopanib and everolimus in the changing metastatic renal cell carcinoma treatment landscape. Future Oncology May 2017
  7. Cathleen Nientiedt, Martina Heller, Volker Endris, Anna-Lena Volckmar, Stefanie Zschäbitz, Maria Tapia-Laliena, Anette Duensing, Dirk Jaeger, Peter Schirmacher, Holger Sültmann, Albrecht Stenzinger, Markus Hohenfellner, Carsten Grüllich#, and Stefan Duensing#. Mutations in BRCA2 and taxane resistance in prostate cancer # shared senior authors Nature scientific reports in press
  8. Friederike Scharhag-Rosenberger, Joachim Wiskemann, Sonia Vallet, Martin Georg Haag, Emanuel Schembri, Dirk Jäger, Carsten Grüllich. Resistance training as supportive measure in advanced cancer patients undergoing TKI therapy a controlled feasibility trial. Supportive Care in Cancer 2017 in press.

Clinical Activities

  • Multidisciplinary Tumor boards
  • Multidisciplinary outpatient and inpatient service
  • Personalized treatment based on genetic analysis within and outside clinical trials
  • Personalized immunotherapies within and outside clinical trials

The Uro-Oncology program focusses on both cutting edge molecular and immunotherapeutic strategies for personalized tumor treatment. Tumor heterogeneity and target detection is one major aim (Höfflin et al (Nature communications 2016). The MORE trial (Dietz et al, Oncotarget 2017) is an ongoing IIT for patients with renal cell cancer. It is the first trial to show the clonal evolution of cancer cell progressing on TKI therapy with the aim of a better tailoring of targeted therapy. Another major achievement is the development of a homologous DNA repair damage panel for prostate cancer patients with high risk disease. This panel can identify BRCAness within the tumor a condition associated with a worse response to chemotherapy (Nientiedt et al. Nature scientific reports 2017) and a target population for the treatment with PARP inhibitors (Nientiedt et al. Ann. Oncology 2016). In Platinum refractory germ cell cancer a trial has been designed for  treating these patients with a PD1 checkpoint inhibitor immunotherapy (Zschaebitz et al Ann. Oncology 2016) resulting in major responses in selected patients (Zschaebitz et al. European Journal of Cancer 2017).

Preclinical Activities

Molecular Urooncology in collaboration with the Sültmann lab, the Schlesner lab and the Stenzinger lab:

  • Whole exome sequencing, mutational signatures, analysis of clonal phylogeny, multiregion reconstruction of clonal evolution
  • Panel next generation sequencing to detect DNA repair defects in prostate cancer

The pre-clinical research programs in Uro-oncology focus on a better understanding of genomic instability, intratumoral heterogeneity and therapy resistance in prostate and renal cancer. Major achievements are the identification of spatial niches as driving forces for intratumoral heterogeneity in renal cancer (Hoefflin et al., 2016) and an in-depth analysis of DNA-repair gene defects in prostate cancer (Nientiedt et al., 2017). In vivo and in vitro studies to characterize mechanisms of antiandrogen and chemotherapy resistance as well as phenotypic drug screens also part of the pre-clinical research program (Zhou et al., Neoplasia 2014; Schneider et al., Urol. Oncol. 2015; Mang et al., Urol. Oncol. 2017).