FOR 2127:  Selection and Adaptation during Metastatic Cancer Progression

• Subject Area: Medicine
• Term: from 2014 to 2022
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 242727105

Aim of the Research Unit is a systematic analysis of systemic cancer progression. We will focus on evolutionary processes that drive colony formation and growth of a metastasis as well as the development of drug resistance.
We will investigate how cancer cells escape intrinsic (cellular failsafe) as well as extrinsic control mechanisms during metastasis. To this end, the different partners will provide state-of-the-art technologies to study genomic, epigenomic and transcriptomic alterations, which allow a comprehensive assessment of cellular deregulation. These alterations will then be put into context of cellular lineage trees that we will generate for individual patients or mice.
In addition, we will investigate the cellular interactions between cancer cells and immune cells or cells forming the metastatic niche. For the first funding period, we will focus on the identification of fundamental principles in two mouse models of cancer, one for breast cancer and one for melanoma. Subsequently, we will proceed to human samples to test specific hypotheses and translate findings from models.

• DFG Programme: Research Units
• International Connection: Israel

Projects

• Administration of the FOR (Applicant Klein, Christoph )
• Bioinformatic core unit (Applicant Spang, Rainer )
• Cell lineage analysis of metastatic desease (Applicant Shapiro, Ehud )
• Computational identification of driver mutations (Applicant Spang, Rainer )
• Coordination Funds (Applicant Klein, Christoph )
• CYLD-a potential mediator of site-specific melanoma metastasis (Applicants Bosserhoff, Anja-Katrin ;  Kuphal, Silke )
• Ectopic somatic progression of metastatic breast cancer cells (Applicant Klein, Christoph )
• Evolution of genetic & epigenetic aberrations during malignant progression of breast cancer and the impact of the local environment (Applicant Rehli, Michael )
• Identification of tumor-cell intrinsic and microenvironmental factors influencing lymph node colonization in melanoma. (Applicants Haferkamp, Ph.D., Sebastian ;  Werner-Klein, Melanie )
• Impact of macrophage/microglia IL4R-activation on CNS-colonization (Applicant Pukrop, Tobias )
• Induction of local and systemic immune tolerance towards tumor metastasis through ectopic gene expression in antigen presenting cells of the bone marrow (Applicant Beckhove, Philipp )
• Innate Immunosurveillance of Metastatic Disease (Applicants Geissler, Ph.D., Edward K. ;  Renner, Philipp )
• Modelling DNA methylation in the systemic progression of cancer (Applicants Rehli, Michael ;  Spang, Rainer )
• Role of hepatic stellate cells in the selection and adaptation of metastasizing cancer cells in the hepatic environment (Applicants Hellerbrand, Claus ;  Lang, Sven Arke )
• Systematic analysis of metastatic cancer: Central mouse and in vitro projects (Applicants Braun, Armin ;  Klein, Christoph )
• The role of non-coding RNAs in metastasis and therapy escape (Applicants Hackl, Christina Elisabeth ;  Meister, Gunter )

• Spokesperson: Professor Dr. Christoph Klein