ChemBIon project description
KCa3.1 channels in tumour pathophysiology
KCa3.1 channels belong to the family of Ca2+-sensitive K+ channels. Their pharmacological properties are well characterised so that several KCa3.1 channel modulators with nanomolar affinities are available. They can serve as tool compounds for the development of imaging probes selectively labelling KCa3.1 channels. KCa3.1 channels are involved in a variety of (patho-)physiological functions. Thus, they are important players in cancer (stroma) cells. Their altered expression in tumours is closely linked to the aggressiveness of the disease. This is at least in part due to the fact that KCa3.1 channels are important regulators of the aggressive cancer cell behaviour (e.g. migration / chemotaxis, proliferation / apoptosis) and because they are involved in the metastatic spread. Accordingly, the targeting of KCa3.1 channels in tumour therapy is now being evaluated as a novel strategy to overcome the development of therapy resistance. These efforts are supported by molecular modelling approaches to develop further specific channel modulators. In addition, imaging probes derived from these modulators will allow the analysis of the localisation and density of KCa3.1 channels in tumour cells with a view to monitoring disease progression.