Targeting calcium signaling in cancer therapy

Abstract

The intracellular calcium ions (Ca ²⁺) act as second messenger to regulate gene transcription, cell proliferation, migration and death. Accumulating evidences have demonstrated that intracellular Ca ²⁺ homeostasis is altered in cancer cells and the alteration is involved in tumor initiation, angiogenesis, progression and metastasis. Targeting derailed Ca ²⁺ signaling for cancer therapy has become an emerging research area. This review summarizes some important Ca ²⁺ channels, transporters and Ca ²⁺-ATPases, which have been reported to be altered in human cancer patients. It discusses the current research effort toward evaluation of the blockers, inhibitors or regulators for Ca ²⁺ channels/transporters or Ca ²⁺-ATPase pumps as anti-cancer drugs. This review is also aimed to stimulate interest in, and support for research into the understanding of cellular mechanisms underlying the regulation of Ca ²⁺ signaling in different cancer cells, and to search for novel therapies to cure these malignancies by targeting Ca ²⁺ channels or transporters.

Graphical abstract

Ca ²⁺ plays vital roles in normal cell physiology, such as gene transcription, cell proliferation and migration. Abnormal Ca ²⁺ signaling by virtue of altered channel expression or activation contributes to carcinogenesis and promotes tumor development. Targeting the dysregulated Ca ²⁺ channels/transporters/pumps may provide a promising chemotherapy for cancer treatment.