Calcium electroporation in cutaneous metastases – A non-randomised phase II multicentre clinical trial

Vissing, Mille; Pervan, Mascha; Pløen, John; Schnefeldt, Mazen; Rafaelsen, Søren Rafael; Jensen, Lars Henrik; Rody, Achim; Gehl, Julie

doi:10.1016/j.ejso.2023.04.024

Cited by 6 publications

(3 citation statements)

References 37 publications

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“…This conjunction, also described as electrochemotherapy, allows the application of significant lower chemotherapeutic doses due to the locally potentiated cytotoxic effect of the agents [30]. Furthermore, EP in combination with calcium ions was proposed as a novel anticancer treatment with emphasis on the avoidance of the harmful systemic effects of chemotherapeutic drugs [31][32][33]. The increased influx of calcium ions induces an intracellular calcium overload, which can cause cell death of cancer cells without significantly damaging surrounding structures and cells.…”

Section: Introductionmentioning

confidence: 99%

“…The increased influx of calcium ions induces an intracellular calcium overload, which can cause cell death of cancer cells without significantly damaging surrounding structures and cells. Furthermore, disruptions in calcium homeostasis have been observed in cancer cells and can lead to detrimental effects, including mitochondrial dysfunction and acute ATP depletion [31,32,34]. Although ECT has already been established as an adjuvant therapeutic option for solid tumors, including cutaneous melanoma, the modality has not been adequately researched for its application and potency in UM.…”

Section: Introductionmentioning

confidence: 99%

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Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model

Tsimpaki,

Anastasova,

Liu

et al. 2024

IJMS

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Despite recent advancements in the diagnosis and treatment of uveal melanoma (UM), its metastatic rate remains high and is accompanied by a highly dismal prognosis, constituting an unmet need for the development of novel adjuvant therapeutic strategies. We established an in vivo chick chorioallantoic membrane (CAM)-based UM xenograft model from UPMD2 and UPMM3 cell lines to examine its feasibility for the improvement of selection of drug candidates. The efficacy of calcium electroporation (CaEP) with 5 or 10 mM calcium chloride (Ca) and electrochemotherapy (ECT) with 1 or 2.5 µg/mL bleomycin in comparison to monotherapy with the tested drug or electroporation (EP) alone was investigated on the generated UM tumors. CaEP and ECT showed a similar reduction of proliferation and melanocytic expansion with a dose-dependent effect for bleomycin, whereas CaEP induced a significant increase of the apoptosis and a reduction of vascularization with varying sensitivity for the two xenograft types. Our in vivo results suggest that CaEP and ECT may facilitate the adequate local tumor control and contribute to the preservation of the bulbus, potentially opening new horizons in the adjuvant treatment of advanced UM.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model

Tsimpaki,

Anastasova,

Liu

et al. 2024

IJMS

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“…The effect of CaEP has been shown to be comparable to ECT using bleomycin in the treatment of cutaneous breast cancer and malignant melanoma metastasis, in smaller phase II trials ( 9 , 10 ). In addition, CaEP has been investigated in phase I–II studies on cutaneous metastases across cancer histologies, in patients with recurrent head and neck cancer, in patients with oesophageal cancer, and in colorectal cancer ( 11 – 14 ). No previous study has reported on the effect of CaEP for BCC.…”

mentioning

confidence: 99%

An Explorative Study on Calcium Electroporation for Low-risk Basal Cell Carcinoma

Wiegell,

Hendel,

Fuchs

et al. 2024

Acta Derm Venereol

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In electrochemotherapy, permeabilization of the cell membrane by electric pulses increases the anti-tumour effect of chemotherapeutics. In calcium electroporation, chemotherapy is replaced by calcium chloride with obvious benefits. This study explores the effect and underlying mechanisms of calcium electroporation on basal cell carcinomas using either high- or low-frequency electroporation. Low-risk primary basal cell carcinomas were treated in local anaesthesia with intratumoral calcium chloride followed by electroporation with high (167 kHz) or low (5 kHz) frequencies. Non-complete responders were retreated after 3 months. The primary endpoint was tumour response 3 months after last calcium electroporation. Plasma membrane calcium ATPase was examined in various cell lines as plasma membrane calcium ATPase levels have been associated with calcium electroporation efficacy. Twenty-two out of 25 included patients complete the study and 7 of these (32%) achieved complete response at 3 months with no difference in efficacy between high- and low-frequency pulses. High-frequency calcium electroporation was significantly less painful (p=0.03). Plasma membrane calcium ATPase was increased 16–32-fold in basal cell carcinoma cell lines compared with 4 other cancer cell lines. Calcium electroporation for low-risk basal cell carcinomas does not fulfil the requirements of a new dermatological basal cell carcinoma treatment but may be useful as adjuvant treatment to surgery in more advanced basal cell carcinomas. The elevated PMCA levels in basal cell carcinomas may contribute to low efficacy.

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The comparison of the dynamics of Ca2+ and bleomycin intracellular delivery after cell sonoporation and electroporation in vitro

Maciulevičius,

Palepšienė,

Vykertas

et al. 2024

Bioelectrochemistry

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Calcium electroporation in cutaneous metastases – A non-randomised phase II multicentre clinical trial

Cited by 6 publications

References 37 publications

Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model

Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model

An Explorative Study on Calcium Electroporation for Low-risk Basal Cell Carcinoma

The comparison of the dynamics of Ca2+ and bleomycin intracellular delivery after cell sonoporation and electroporation in vitro

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