Cancer is in its essence a disease of miscommunication. The failure of tumor cells to communicate correctly internally is caused by genetic and epigenetic events that lead to excessive cell growth. In addition, and perhaps equally important for the etiology of cancer, malignant cells engage in intercellular communication with various cell types populating their micro- and macroenvironment. Thus, a tumor should be considered as a communicating organ in its own right comprising multiple cell types that collectively evolve into a clinically manifested and deadly disease.
It is increasingly appreciated that cancer results from the concerted performance of genetically altered tumor cells interacting with ostensibly normal cells in the microenvironment. The tumor cell-centric view of cancer that has been prevalent during the past decades of research does not take into account the context in which malignant cells subsist. As the cancer progresses, the surrounding microenvironment co-evolves into an activated state through continuous paracrine communication, thus creating a dynamic signaling circuitry that promotes cancer initiation and progression, and ultimately leads to a fatal disease. In addition, we propose that the tumor microenvironment is a critical determinant of treatment outcome. Thus, as a rich source of growth-promoting factors, the tumor stroma is an underestimated target for the development of biomarkers and therapeutic modalities.
We aim to molecularly map the support functions performed by the various cell types comprising the tumor microenvironment. We believe that decisive treatment benefit can only be achieved by targeting distinct cell types and pathways that collectively sustain tumor growth.
Specifically, molecular interactions between cancer-associated fibroblasts, pericytes and endothelial cells are explored with a special focus on novel anti-cancer strategies. Importantly, the cellular networks within tumors cannot be studied in isolation. Thus, our work ranges over many different topics, with methodology, technology and purpose as the common denominators.
We currently pursue three main avenues of research:
Identification of new cellular subsets of the tumor stroma and their influence on cancer progression
Investigation of the therapeutic utility of the tumor stroma
Exploration of the tumor stroma as biomarkers of prognosis or response to therapy in human cancer
Taken together, the overall aim of our work is to generate basic knowledge about the interdependent way cells within a tumor relate to each other, as well as produce information that will be immediately useful for the design and modification of clinical practice.