T-type calcium channels blockers as new tools in cancer therapies.
T-type calcium channels are involved in a multitude of cellular processes, both physiological and pathological, including cancer. T-type channels are also often aberrantly expressed in different human cancers and participate in the regulation of cell cycle progression, proliferation, migration, and survival. Here, we review the recent literature and discuss the controversies, supporting the role of T-type Ca(2+) channels in cancer cells and the proposed use of channels blockers as anticancer agents. A growing number of reports show that pharmacological inhibition or RNAi-mediated downregulation of T-type channels leads to inhibition of cancer cell proliferation and increased cancer cell death. In addition to a single agent activity, experimental results demonstrate that T-type channel blockers enhance the anticancer effects of conventional radio- and chemotherapy. At present, the detailed biological mechanism(s) underlying the anticancer activity of these channel blockers is not fully understood. Recent findings and ideas summarized here identify T-type Ca(2+) channels as a molecular target for anticancer therapy and offer new directions for the design of novel therapeutic strategies employing channels blockers. Physiological relevance: T-type calcium channels are often aberrantly expressed or deregulated in cancer cells, supporting their proliferation, survival, and resistance to treatment; therefore, T-type Ca(2+) channels could be attractive molecular targets for anticancer therapy.
Department of Radiation Oncology, University of Virginia, PO Box 800383, Charlottesville, VA, 22908, USA.
Barbara
B
Dziegielewska
Lloyd S
LS
Gray
Jaroslaw
J
Dziegielewski
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D020747:Calcium Channels, T-Type / Q000096:biosynthesis* / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D015316:Genetic Therapy / Q000639:trends; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy
D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type