Ion Channel Signalling in Cancer: From Molecular Mechanisms to Therapeutics

Mammalian cells are equipped with a large number of ion channels with diverse activation mechanisms and/or modalities. Ion channels are mainly located in the plasma membrane and thus serve crucial molecular mechanisms that transduce extracellular physical, biochemical or biological signals to intracellular events via mediating the movement of ions, particularly Ca²⁺ entry to elevate the intracellular Ca²⁺ level. Ion channels are also found in the membrane of intracellular organelles and regulate the ion homeostasis in such intracellular compartments as well as the cytosol. As such, ion channels play an important role in a wide range of physiological processes, which are not restricted to cell excitability.

Accumulating evidence show that alterations in the expression and/or function of both the ion-forming or auxiliary subunits occur in neoplastic and malignant cells, markedly influencing cell apoptosis, proliferation, migration and invasion. In addition, ion channels significantly modulate the function of other cells present in the tumour microenvironments, such as endothelial cells that form new blood vessels to support cancer cell proliferation and migration, anti-tumour or tumour-supporting immune cells, and fibroblasts or other stroma cells modulating the composition and stiffness of tumour matrix and immune responses. Collectively, altered expression and function of ion channels are critical in determining tumour growth, angiogenesis, metastasis, and even resistance to treatments. Ion channels are well-characterized targets in several pathophysiological conditions. There is a growing interest in ion channels as attractive cancer biomarkers as well as therapeutic targets to treat cancers.

This Research Topic aims to provide a forum for researchers to share new research or concepts and recent progress that facilitate a better understanding of how ion channels play a role in driving oncological conditions and also identification of specific ion channels as biomarkers as well as drug targets to improve the existing treatments and develop novel anti-cancer therapies. The scope of this Topic includes, but is not limited to: profiling ion channel expression and functions in solid and leukemic malignancies aiming identification of new diagnostic and prognostic markers including protein and mRNA expression and genetic linkage/association of SNPs in ion channel-encoding genes; role of ion channels in cancer cell death, in tumour transformation and neoplasic cell proliferation, in cancer cell migration, angiogenesis and metastatic spreading, and in cancer stem cell properties; role of ion channels in tumour-host crosstalk including interaction with immune and stromal cells; role of ion channels in cancer resistance to current therapeutic regimens; pharmacological interventions with ion channel modulators to suppress cancer growth and dissemination; clinical trials targeting ion channels to treat cancer patients.