Calcium transport and signalling in breast cancer: Functional and prognostic significance

Comprised of a complex network of numerous intertwining pathways, the Ca²⁺ signalling nexus is an essential mediator of many normal cellular activities. Like many other such functions, the normal physiological activity of Ca²⁺ signalling is frequently co-opted and reshaped in cases of breast cancer, creating a potent oncogenic drive within the affected cell population. Such modifications can occur within pathways mediating either Ca²⁺ import (e.g. TRP channels, ORAI-STIM1) or Ca²⁺ export (e.g. PMCA), indicating that both increases and decreases within cellular Ca²⁺ levels have the potential to increase the malignant potential of a cell. Increased understanding of these pathways may offer clinical benefit in terms of both prognosis and treatment; patient survival has been linked to expression levels of certain Ca²⁺ transport proteins, whilst selective targeting of these factors with novel anti-cancer agents has demonstrated a variety of anti-tumour effects in in vitro studies. In addition, the activity of several Ca²⁺ signalling pathways has been shown to influence chemotherapy response, suggesting that a synergistic approach coupling traditional chemotherapy with Ca²⁺ targeting agents may also improve patient outcome. As such, targeted modulation of these pathways represents a novel approach in precision medicine and breast cancer therapy.