Genomes and Genes
Affiliation: University Hospital
- GDC-0449--targeting the hedgehog signaling pathwayChristine Dierks
Department of Hematology and Oncology, Freiburg University Medical Center, Hugstetterstrasse 55, 79106, Freiburg, Germany
Recent Results Cancer Res 184:235-8. 2010..It was successfully tested in a phase-I clinical trial demonstrating good pharmacodynamic (PD) and pharmacokinetic (PK) properties and showing objective response and clinical benefit in several patients with basal cell carcinoma...
- Expansion of Bcr-Abl-positive leukemic stem cells is dependent on Hedgehog pathway activationChristine Dierks
Department of Hematology Oncology, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany
Cancer Cell 14:238-49. 2008..Pharmacological Smo inhibition reduced LSCs in vivo and enhanced time to relapse after end of treatment. Our results indicate that Smo inhibition might be an effective treatment strategy to reduce the LSC pool in CML...
- The ITK-SYK fusion oncogene induces a T-cell lymphoproliferative disease in mice mimicking human diseaseChristine Dierks
Hematology Oncology, University of Freiburg, Freiburg, Germany
Cancer Res 70:6193-204. 2010..Therefore, pharmacologic inhibition of SYK in patients with U-PTCLs carrying the ITK-SYK fusion protein might be an effective treatment strategy...
- Spleen tyrosine kinase inhibition prevents chemokine- and integrin-mediated stromal protective effects in chronic lymphocytic leukemiaMaike Buchner
Department of Hematology and Oncology, University Medical Center Freiburg, Freiburg, Germany
Blood 115:4497-506. 2010..SYK blockade in CLL is a promising therapeutic principle not only for its inhibition of the BCR signaling pathway, but also by inhibiting protective stroma signals in a manner entirely independent of BCR signaling...
- Insulin-like growth factor-1 receptor (IGF1R) as a novel target in chronic lymphocytic leukemiaNiuscha Yaktapour
Department of Hematology Oncology, University Medical Center Freiburg, Freiburg, Germany
Blood 122:1621-33. 2013..Importantly, IGF1R inhibitors compromise CLL viability in their microenvironment context, implicating this RTK as a promising therapeutic target. ..
- Trisomy 12 and elevated GLI1 and PTCH1 transcript levels are biomarkers for Hedgehog-inhibitor responsiveness in CLLSarah Decker
Department of Hematology Oncology, University Medical Center Freiburg, Hugstetter Strasse 55, Freiburg, Germany
Blood 119:997-1007. 2012....
- Ptch2 loss drives myeloproliferation and myeloproliferative neoplasm progressionClaudius Klein
Department of Hematology Oncology, University Medical Center Freiburg, D 79106 Freiburg, Germany Institute for Molecular Medicine and Cell Research, University of Freiburg, D 79104 Freiburg, Germany
J Exp Med 213:273-90. 2016..Our findings suggest HH ligand inhibitors as possible drug candidates that act on hematopoiesis and the niche to prevent transformation of MPNs into leukemias. ..
- The microenvironment differentially impairs passive and active immunotherapy in chronic lymphocytic leukaemia - CXCR4 antagonists as potential adjuvants for monoclonal antibodiesMaike Buchner
Department of Haematology and Oncology, University Medical Centre Freiburg, Freiburg, Germany
Br J Haematol 151:167-78. 2010..Our data identify the combination of CXCR4 antagonists with passive - but not active - immunotherapy as a promising potential treatment concept in CLL...
- Spleen Tyrosine Kinase Is Involved in the CD38 Signal Transduction Pathway in Chronic Lymphocytic LeukemiaMarco Benkisser-Petersen
Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
PLoS ONE 11:e0169159. 2016..Finally, we observed a clear correlation between CD38 expression on CLL cells and SYK-inhibitor efficacy. In conclusion, our study provides deeper mechanistic insight into the effect of SYK inhibition in CLL...
- Spleen tyrosine kinase is overexpressed and represents a potential therapeutic target in chronic lymphocytic leukemiaMaike Buchner
University Medical Center Freiburg, Department of Hematology and Oncology, Germany
Cancer Res 69:5424-32. 2009..Combination of SYK inhibitors with fludarabine might be a novel treatment option particularly for CLL patients with poor prognosis and should be further evaluated in clinical trials...
- PIM kinases are essential for chronic lymphocytic leukemia cell survival (PIM2/3) and CXCR4-mediated microenvironmental interactions (PIM1)Sarah Decker
Authors Affiliations Department of Hematology Oncology Centre of Chronic Immunodeficiency, University Medical Centre Freiburg Faculty of Biology BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany Department of Biomedicine, University Hospital Basel, Basel, Switzerland Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School Department of Cancer Biology, Dana Faber Cancer Institute, Boston, Massachusetts and Department of Hematology, Leiden University Medical Centre, Leiden, The Netherlands
Mol Cancer Ther 13:1231-45. 2014....
- MPN patients harbor recurrent truncating mutations in transcription factor NF-E2Jonas S Jutzi
Department of Hematology Oncology, University Hospital Freiburg, 79106 Freiburg, Germany
J Exp Med 210:1003-19. 2013..NF-E2 mutant cells acquire a proliferative advantage, witnessed by clonal dominance over WT NF-E2 cells in MPN patients. Our data underscore the role of increased NF-E2 activity in the pathophysiology of MPNs...