Tumor cell metabolism and epigenetic regulation in the development of new therapeutic approaches for colorectal and pancreatic cancer

Working group Conradi

Colorectal Cancer

While great success has been achieved for the treatment of colorectal cancer (CRC) during the last decades, there is still great need for improvement as prognosis is limited by the development of resistance towards established anti-tumor therapies and due to the development of metastasis during the course of disease. In addition to conventional chemo- and radiotherapy, anti-angiogenic therapies such as VEGF signaling inhibition have partly proven to be effective in the treatment of (m)CRC, however these strategies are strongly limited by cellular resistance mechanisms.

Currently in our lab, in vivo patient derived xenograft models and in vitro cultures using patient derived organoids and cell lines are being used to test new therapeutic strategies, combining the concept of tumor vessel normalization by metabolic targeting of tumor endothelial cells together with chemoradiotherapy. 

These experimental approaches aid to understand not only the effects of cellular metabolism and epigenetic regulation on cancer cells but also how the tumor microenvironment (and especially the endothelium) influences the development of cancer resistance. 

The projects developed in our group are future-oriented translational research projects, with the aim to develop new stategies in the area of gastrointestinal cancer research and treatment options in the field of metabolism-based anti-tumor therapies. 

Our research team is especially interested in the underlying mechanisms involved in tumor angiogenesis. The current research projects are designed to: (i) better comprehend the molecular mechanisms by which tumor cells trigger angiogenesis; (ii) investigate the metabolic pathways which can promote tumor vessel formation versus tumor vessel co-option; (iii) to find novel therapeutical targets for the treatment of cancer and (iv) to develop and evaluate new strategies that can undermine tumor resistance towards therapy.

Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) remains a major challenge in cancer medicine with adesperate need to develop better treatment strategies. In fact, despite significant research efforts, PDAC still displays the highest mortality rate among all solid tumors in mankind. Major causes for its devastating disease outcome are the exceptionally aggressive tumor biology and the remarkable resistance to conventional anti-tumor treatments. Both characteristics are mechanistically linked to a very high degree of tumor heterogeneity, which is reflected by recent identification of various molecular and phenotypic PDAC subtypes.

Our research team is interested in the molecular mechanisms involved in specific metabolic PDAC subtypes (glycolytic versus lipolytic) and how they might contribute to tumor progression and therapy resistance. Ultimately our goal is to explore possible PDAC metabolic vulnerabilities which in turn might contribute to better therapies. The current research projects are designed to: (i) characterize different PDAC patient-derived organoids and cancer cell lines’ metabolic subtypes; (ii) to test the effects of novel PFKFB3 glycolytic inhibitors on PDAC cancer organoids and patient-derived xenografts; (iii) to find novel therapeutical targets for the treatment of PDAC that can undermine tumor resistance towards therapy. For further information, please also visit the Clinical Research Unit CRU5002 website.

Lab members

  • PD Dr. Dr. Lena-Christin Conradi – group leader
  • Dr. Tiago De Oliveira – postdoc
  • Mrs. Birgit Jünemann – technical assistant
  • Mr. Nikola Dobriniv Kyuchukov, B.A. – MD candidate
  • Mr. Johannes Robert Fleischer – MD candidate
  • Ms. Shuang Fan – MD candidate
  • Mr. Olaf Schulze – MD candidate
  • Ms. Teona Midelashvili – PhD student
  • Ms. Alexandra M. Schmitt – MD candidate
  • Ms. Dorothée Sartorius – MD candidate
  • Ms. Chiara Jodszuweit – MD candidate
  • Ms. Linde-Allegra Rosen – MD candidate

Lab alumni

  • Ms. Gwendolyn Haas – MD candidate
  • Ms. Tina Goldhardt – MD candidate
  • Mr. Marcus Edelmann – MD candidate

Publications

  • An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates.
    Goveia J, Rohlenova K, Taverna F, Treps L, Conradi LC, Pircher A, Geldhof V, de Rooij LPMH, Kalucka J, Sokol L, García-Caballero M, Zheng Y, Qian J, Teuwen LA, Khan S, Boeckx B, Wauters E, Decaluwé H, De Leyn P, Vansteenkiste J, Weynand B, Sagaert X, Verbeken E, Wolthuis A, Topal B, Everaerts W, Bohnenberger H, Emmert A, Panovska D, De Smet F, Staal FJT, Mclaughlin RJ, Impens F, Lagani V, Vinckier S, Mazzone M, Schoonjans L, Dewerchin M, Eelen G, Karakach TK, Yang H, Wang J, Bolund L, Lin L, Thienpont B, Li X, Lambrechts D, Luo Y, Carmeliet P.Cancer Cell. 2020 Jan 13;37(1):21-36.e13. doi: 10.1016/j.ccell.2019.12.001.

Contact

Group leader

PD Dr. Lena Conradi

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