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T-type calcium channels blockers as new tools in cancer therapies

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Abstract

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 Ca2+ 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 Ca2+ 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 Ca2+ channels could be attractive molecular targets for anticancer therapy.

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Acknowledgments

This work was supported in part by the University of Virginia P30 CA44579, by a pilot funding from the James and Rebecca Craig Fund (to JD), and by the University of Virginia Department of Radiation Oncology George P. Amorino pilot grant (to BD and JD).

Conflict of interest

Dr. Lloyd S. Gray is a cofounder of and consultant to Tau Therapeutics LLC. Dr. Jaroslaw Dziegielewski has received research contract funding from Tau Therapeutics LLC.

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Virginia, PO Box 800383, Charlottesville, VA, 22908, USA

    Barbara Dziegielewska & Jaroslaw Dziegielewski

  2. Tau Therapeutics LLC, Charlottesville, VA, USA

    Lloyd S. Gray

  3. Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, VA, USA

    Jaroslaw Dziegielewski

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  1. Barbara Dziegielewska
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  2. Lloyd S. Gray
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Correspondence to Jaroslaw Dziegielewski.

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This article is published as part of the Special Issue on T-type (Cav3) calcium channels in health and disease.

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Dziegielewska, B., Gray, L.S. & Dziegielewski, J. T-type calcium channels blockers as new tools in cancer therapies. Pflugers Arch - Eur J Physiol 466, 801–810 (2014). https://doi.org/10.1007/s00424-014-1444-z

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