Heat-shock protein 90 (Hsp90) blockade as a therapeutic approach for modulating tumor metabolism and angiogenesis in cancer

• Applicant: Professor Dr. Sven Arke Lang
• Subject Area: Hematology, Oncology
• Term: from 2011 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 190230491

• Final Report Year: 2019

Final Report Abstract

Results from our experiments showed novel insights into the effects of Hsp90 blockade on cancer metabolism with special emphasis on HK II in cancer cells. Although Hsp90 blockade did not affect angiogenesis in the FGF/FGFR system as we suggested, we assessed the efficacy of targeting the FGFR system in several cancer models, including the effects on angiogenesis and tumor stroma. Finally, we determined STAT5b as a novel target on human pancreatic cancer via effects on metabolism and angiogenesis.

Publications

• 2011. Targeting FGFR/PDGFR/VEGFR impairs tumor growth, angiogenesis, and metastasis by effects on tumor cells, endothelial cells, and pericytes in pancreatic cancer. Molecular Cancer Therapeutics 10: 2157-2167
  Taeger, J., C. Moser, C. Hellerbrand, M. E. Mycielska, G. Glockzin, H. J. Schlitt, E. K. Geissler, O. Stoeltzing, and S. A. Lang
  (See online at https://doi.org/10.1158/1535-7163.mct-11-0312)
• (2012) Contrast-enhance ultrasound (CEUS) detects effects of vascular disrupting therapy in an experimental model of gastric cancer. Clinical hemorheology and microcirculation. Clin Hemorheol Microcirc.
  Lang, S. A., C. Moser, S. Gehmert, K. Pfister, C. Hackl, A. A. Schnitzbauer, C. Stroszczynski, H. J. Schlitt, E. K. Geissler, and E. M. Jung
  (See online at https://doi.org/10.3233/CH-121658)
• (2012) STAT5b as molecular target in pancreatic cancer--inhibition of tumor growth, angiogenesis, and metastases. Neoplasia 14: 915-925
  Moser, C., P. Ruemmele, S. Gehmert, H. Schenk, M. P. Kreutz, M. E. Mycielska, C. Hackl, A. Kroemer, A. A. Schnitzbauer, O. Stoeltzing, H. J. Schlitt, E. K. Geissler, and S. A. Lang
  (See online at https://doi.org/10.1593/neo.12878)
• (2012) Targeting HSP90 by the novel inhibitor NVP-AUY922 reduces growth and angiogenesis of pancreatic cancer. Anticancer Research 32: 2551-2561
  Moser, C., S. A. Lang, C. Hackl, C. Wagner, E. Scheiffert, H. J. Schlitt, E. K. Geissler, and O. Stoeltzing
  
• 2012. Oncogenic MST1R activity in pancreatic and gastric cancer represents a valid target of HSP90 inhibitors. Anticancer Research 32: 427-437
  Moser, C., S. A. Lang, C. Hackl, H. Zhang, K. Lundgren, V. Hong, A. McKenzie, B. Weber, J. S. Park, H. J. Schlitt, E. K. Geissler, Y. D. Jung, and O. Stoeltzing
  (See online at https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.926.8929&rep=rep1&type=pdf)