-
Title:
Calcium electroporation; From initial discovery to clinical use
Authors:
Gehl, Julie
Department of Clinical Oncology and Palliative Care
Zealand University Hospital
4000 Roskilde, Denmark
and
Department of Clinical Medicine
Faculty of Health and Medical Sciences
University of Copenhagen, Denmark
Abstract:
A decade ago, the first paper describing calcium electroporation as a potential cancer treatment was published [1], describing how internalization of supra-physiological doses of calcium, using electroporation, could lead to cancer cell death associated with acute and severe ATP-depletion. In 2017 and 2018 the results of the first clinical studies were published [2, 3]. Since then, calcium electroporation has been investigated in clinical trials on head and neck cancer, esophageal cancer, colorectal cancer, and in reported in case reports from patients with gynecological cancer and lymphoma. Studies from patients with cutaneous metastases include in particular data from patients with breast cancer, but also malignant melanoma, lung cancer and gynecological cancer. Studies on benign or premalignant conditions have also been published, as calcium has an advantage of not giving rise to mutagenic effects. Finally, veterinary studies add to body of evidence.
Alongside the extension of clinical data, a number of studies have looked at calcium electroporation at the cellular level in terms of mechanism of action [4], as well as an immune effect observed both animal and human studies.
The mechanism of action of calcium electroporation and electrochemotherapy is quite different, and recent observations suggest that it is possible to change from one method to the other if needed.
Calcium is a very inexpensive drug which is easy to use. The technology may also be combined with e.g. gene therapy to obtain potentiation of an immune response, or with irreversible electroporation to obtain a wider treatment field.
This review of current knowledge intends to lay out the current knowledge on mechanisms of action at the cellular level, the reasoning behind dosing regimens, as well describe the many clinical studies and explore further developments.
Keywords:
Calcium electroporation
Refs:
Frandsen SK, Gissel H, Hojman P, et al. Direct therapeutic applications of calcium electroporation to effectively induce tumor necrosis. Cancer Res. 2012 Mar 15;72(6):1336-41.
2. Falk H, Lambaa S, Johannesen HH, et al. Electrochemotherapy and calcium electroporation inducing a systemic immune response with local and distant remission of tumors in a patient with malignant melanoma - a case report. Acta Oncol. 2017 Aug;56(8):1126-31.
3. Falk H, Matthiessen LW, Wooler G, et al. Calcium electroporation for treatment of cutaneous metastases; a randomized double-blinded phase II study, comparing the effect of calcium electroporation with electrochemotherapy. Acta Oncol. 2018 Mar;57(3):311-9.
4. Frandsen SK, Vissing M, Gehl J. A Comprehensive Review of Calcium Electroporation -A Novel Cancer Treatment Modality. Cancers (Basel). 2020 Jan 25;12(2).
Topic 1:
6. Cancer treatment and tumor ablation
Topic 2:
1. Biological responses (molecular, subcellular, cellular and intercellular)
-
|
