The Ten Dijke group is focused on TGF-β signaling dynamics during cancer progression in both cancer cells and neighbouring stroma, including cancer associated fibroblasts, blood and lymphatic vessels and immune cells. In particular, his laboratory is interested in how TGF-β switches from tumor suppressor at early stages into tumor promoter at late stages; how cancer cells loose the cytostatic response to TGF-β, but use SMAD and non-SMAD signaling pathways to mediate an epithelial to mesenchymal transition, invasion and metastasis of cancer cells. Insights into these mechanisms will be applied to develop therapeutic agents that selectively inhibit the pro-oncogenic effects of TGF-β.
Cancer cells that are treated by chemotherapy or by therapy targeting oncogenic signaling pathways frequently become resistant to therapy by over-activating TGF-β signaling. Thus, combinatorial treatment of such inhibitors with TGF-β inhibitors that target invasion, tumor angiogenesis or its immune suppression will be actively pursued, not only to obtain fundamental new insights, but for translation into the clinic.