Cancer growth and metastasis are strictly dependent on tumor vascularization, which is promoted by the same tumour cells upon secretion of a number of growth factors. Vessel formation is a complex multistep process during which 'activated' endothelial cells (ECs), the first mechanical and functional interface between blood and tissues, proliferate, migrate, differentiate and are stabilized in a new circulatory network.
Despite promising results, emerging data indicate that responses to vascular targeting therapy (VTT) are short-lived and resistance develops in the majority of patients. The discovery of new therapeutic targets is therefore necessary to give a new input to the antiangiogenic therapy. On the other hand membrane channels, as cell surface expressed proteins, are easily and directly accessible via the bloodstream, facilitating intervention with either macromolecular or small molecules compounds.
Being involved in nearly all of the ‘hallmarks of cancer’, there is an increasing consensus on the idea that ion channels play a significant role in driving cancer progression at all stages. Accumulating evidence tends to demonstrate that the development of some cancers could also involve such ion channel aberrations and, therefore, could be classified as channelopathies. Therefore ion channels may be seen as potential novel therapeutic, diagnostic, and prognostic targets for anti-cancer therapies.
Among the different channels, TRP (Transient Receptor Potential) and Orai channels are up or down-regulated in cancer cells and have been suggested as valuable markers in predicting cancer progression and as potential targets for pharmaceutical therapy. In particular several studies from our laboratory show that these channels are key pleayers in prostate cancer cells as well as EC proliferation, migration or apoptosis depending on the type of channel involved.
Our main interest is therefore to study the role of TRP channels regulating Ca2+ signature of tumor angiogenesis during cancer progression and metastasis and also to possibly develop pharmacological tools for the elaboration of effective therapies.
