Stem cells in diseases (cancer stem cells)
Initiators: Andreas Trumpp (Heidelberg) and Thomas Brabletz (Erlangen)
The cancer stem cell (CSC) concept has made a tremendous impact on the way we think about and study cancer progression and metastasis. It states that the cellular heterogeneity displayed by many tumors is explained by a hierarchical organization similar to the way normal regenerative tissues (skin, gastro-intestinal mucosa or the hematopoietic system) are organized. Initially demonstrated for hematopoietic tumors, the CSC concept has proven to be relevant also for many solid cancer entities. Although normal stem cells are often the cells that acquire the first oncogenic mutations, progenitors and perhaps differentiating cell types can also become CSCs by the accumulation of oncogenic lesions, which lead to the acquirement of de-regulated stem cell properties. Importantly, CSCs also inherit or acquire specific features that facilitate their spread through the body via the blood stream or the lymphatic system. Such metastasis initiating cells (MICs) are derived from CSCs and have the clonal capacity to form deadly metastasis. CSCs and MICs display a high degree of resistance to conventional radio-and chemotherapy and are the source of minimal residual disease, tumor recurrence and metastasis.
The overall aim of the working group “Cancer stem cells” is to integrate the knowledge about cancer stem cells in Germany and to transfer this knowledge into clinical practice. To streamline the development of effective applications it is critical to exchange opinions, experience, expertise and resources across the fields of basic, translational and clinical research to answer the following questions:
- How are CSCs defined?
- What is the origin of CSCs (in relation to normal tissue stem cells, generation from differentiated cancer cells, role of plasticity)?
- What is the role of CSCs in tumor initiation, progression, dissemination, dormancy and metastasis?
- What are mechanisms of CSC-related therapy resistance and how to develop strategies to overcome it?
- How do solid and leukemic CSCs compare?
- What is the role of the CSC niche for tumor progression and metastasis?
- What is the link between CSCs, tumor heterogeneity and genetic diversity within tumors?
- What are the necessary technical advances that are currently required to: identify new CSC markers, establish protocols to reliably isolate CSCs, develop easy to manipulate in vitro and in vivo systems?
The GSCN scientific working group on “Stem cells in diseases (cancer stem cells)” aims to provide a forum in which researchers at all levels can search for and find cooperation partners, establish synergies and generate the experimental basis to develop effective therapeutic strategies to eliminate CSCs and to overcome associated therapy resistance, cancer recurrence and metastasis.