Oncogenic Signal Transduction Pathways as Targets for Personalized Tumor Therapy

Most types of human cancer are caused by mutations that deregulate the normal cell proliferation pathways and prevent terminal differentiation. For this reason, cancer research and developmental biology address similar questions: How do genes control cell proliferation, how does a cell switch from a proliferating into a terminally differentiated state, how are superfluous cells eliminated, or how can specific mutations alter the behavior of individual cells?
The intercellular signals and intracellular signal transduction pathways that control the development of all multicellular organisms are frequently mutated and deregulated in human cancers. Thus, research on simple animal model organisms, such as C. elegans (roundworm) or D. melanogaster (fruit fly), significantly contributes to the understanding of genetic and biochemical events leading to cancer formation. Furthermore, many of the techniques and assays commonly used in developmental biology can be applied to study the phenotypes of human tumor cells. Research in mammalian models can extend these concepts and provide further insights such as the influence of the complex tumor microenvironment.
Rather than focusing on individual signaling pathways we will characterize complete signaling networks created by the crosstalk of individual pathways, to understand the complex cellular responses to extrinsic signals. A long-term outcome of this research is that we will better understand the compensatory effects underlying cancer drug resistance of tumor cells and be able to predict the outcome of specific pharmacological interventions at the molecular level. Obtaining this knowledge is an essential requirement for the development of personalized cancer therapies.
The specific aims this project are:

  1. The identification of molecular pathways relevant to tumor cell biology with special emphasis on developmental biology, stem cell biology, tumor cell invasion and metastasis.
  2. The identification of molecular markers that can be used to monitor the progression of cancer through different stages of malignancy and evaluate the cellular responses to drug treatment.
  3. The development of new strategies for therapeutic interventions targeting specific signaling pathways.