Ca²⁺ homeostasis: a potential target for cancer therapies

Calcium ions (Ca²⁺) play a crucial role as secondary messengers in both excitable and non-excitable cells. A complex system of proteins and molecules involved in calcium handling allows Ca²⁺ signals to be transduced. In cancer cells, mutations, aberrant expression, and dysregulation of these calcium handling toolkit proteins disrupt the normal Ca²⁺ flux between extracellular space, cytosol, endoplasmic reticulum and mitochondria, as well as the spatio-temporal patterns of Ca²⁺ signalling. This leads to the dysregulation of calcium-dependent effectors that control key signaling pathways involved in cancer cell proliferation, survival and invasion. Although there has been progressing in understanding the remodelling of calcium homeostasis in cancer cells and identifying key calcium transport molecules that promote malignant phenotypes, much work remains to be done to translate these fundamental findings into new tools for diagnosing and treating cancer by targeting Ca²⁺ homeostasis.