A new concept has emerged in oncology over the last decade: ion channels may act as novel and important regulators of specific steps in cancer progression. The remodeling of the expression/activity of these channels contributes to the neoplastic phenotype from control of cell proliferation and apoptosis to the control of cell migration/invasion and metastatic spread. These channels are therefore novel therapeutic targets and/or prognostic markers in different cancers. Ion channels are easily accessible to chemical modulation constituting potentially useful targets for the development of targeted and personalized innovative anti-cancer therapies. A major advantage is their accessibility from the extracellular side, which makes ion channel modulators particularly effective. Among ion channels, recent studies point to calcium-activated potassium and voltage-independent calcium channels as new and promising targets for anti-cancer therapies. Nevertheless, any investigation of the potential use of these channels for anti-cancer therapies requires prior development of specific ion channel modulators and their validation in appropriate preclinical models. In addition, determination of their clinical relevance is also a crucial step.
Regarding the unique expertise in France, of several internationally recognized teams of the “Grand Ouest” Region in the field of calcium-activated potassium channels and voltage-independent calcium channels involved in cancer, we have united our efforts and expertise within a structuring network named IonChannel-CanceropoleGrandOuest (IC-CGO). Pluridisciplinarity of members (Chemists, biochemists, biologists, Electophysiologists, clinicians, …) allow transversal, complementary and multidisciplinary research from basic research to the clinic.
The key objectives of network are :
To identify the role in carcinogenesis of signaling complexes composed of calcium-activated potassium channels and calcium channels involved in cancer cell migration and survival and regulating calcium homeostasis of tumors cells;
To determine the clinical relevance of these channels in breast cancer, prostate cancer, chronic lymphocytic leukemia and chronic myeloid leukemia;
To discover and develop new active modulators of these channels;
To develop appropriate cellular models for drug screening and ion channel probes for diagnostic and therapeutic approaches;
To test identified compounds on existing in vitro and in vivo platforms from the Canceropole Grand Ouest and;
To create a novel multicentric and integrated screening platform.
We believe that this network that will combine basic and clinical research through collaborations between clinicians, chemists and biologists should allow us to propose calcium-activated potassium channels and voltage independent calcium channels as new relevant drug targets and prognostic indicators for breast cancer, prostate cancer and leukemia. In addition, we believe that these channels will be used to reversed acquired resistance to conventional chemotherapy or targeted therapy. Reversing such resistance is a major challenge in oncology.