Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

Altamura, Concetta; Greco, Maria Raffaella; Carratù, Maria Rosaria; Cardone, Rosa Angela; Desaphy, Jean-François

doi:10.3390/cancers13040668

Cited by 17 publications

(10 citation statements)

References 198 publications

(205 reference statements)

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“…Accordingly, inhibition of metastasis by mAb-nNav1.5 and pAb-nNav1.5 corresponded with downregulation of nSCN5A expression in the tumour tissues. Previously, Gao et al (2019) showed that an antibody targeting adult Nav1.5, E3, exerts an inhibitory effect on tumour growth and invasion in ovarian cancer animal model (Gao et al, 2019) -in ovarian cancer, Nav1.5 is one of the major VGSCs subtype expressed and associated with aggressiveness (Altamura et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Invasion and Metastasis Suppression by Anti-Neonatal Nav1.5 Antibodies in Breast Cancer

Sharudin

Din

Azahar

et al. 2022

Asian Pac J Cancer Prev

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Background: Detectable neonatal Nav1.5 (nNav1.5) expression in tumour breast tissue positive for lymph node metastasis and triple-negative subtype serves as a valid tumour-associated antigen to target and prevent breast cancer invasion and metastasis. Therapeutic antibodies against tumour antigens have become the predominant class of new drugs in cancer therapy because of their fewer adverse effects and high specificity. Objective: This study was designed to investigate the therapeutic and anti-metastatic potential of the two newly obtained anti-nNav1.5 antibodies, polyclonal anti-nNav1.5 (pAb-nNav1.5) and monoclonal anti-nNav1.5 (mAb-nNav1.5), on breast cancer invasion and metastasis. Methods: MDA-MB-231 and 4T1 cells were used as in vitro models to study the effect of pAb-nNav1.5 (59.2 µg/ml) and mAb-nNav1.5 (10 µg/ml) (24 hours treatment) on cell invasion. 4T1-induced mammary tumours in BALB/c female mice were used as an in vivo model to study the effect of a single dose of intravenous pAb-nNav1.5 (1 mg/ml) and mAb-nNav1.5 (1 mg/ml) on the occurrence of metastasis. Real-time PCR and immunofluorescence staining were conducted to assess the effect of antibody treatment on nNav1.5 mRNA and protein expression, respectively. The animals' body weight, organs, lesions, and tumour mass were also measured and compared. Results: pAb-nNav1.5 and mAb-nNav1.5 treatments effectively suppressed the invasion of MDA-MB-231 and 4T1 cells in the 3D spheroid invasion assay. Both antibodies significantly reduced nNav1.5 gene and protein expression in these cell lines. Treatment with pAb-nNav1.5 and mAb-nNav1.5 successfully reduced mammary tumour tissue size and mass and prevented lesions in vital organs of the mammary tumour animal model whilst maintaining the animal's healthy weight. mRNA expression of nNav1.5 in mammary tumour tissues was only reduced by mAb-nNav1.5. Conclusion: Overall, this work verifies the uniqueness of targeting nNav1.5 in breast cancer invasion and metastasis prevention, but more importantly, humanised versions of mAb-nNav1.5 may be valuable passive immunotherapeutic agents to target nNav1.5 in breast cancer.

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Section: Discussionmentioning

confidence: 99%

Invasion and Metastasis Suppression by Anti-Neonatal Nav1.5 Antibodies in Breast Cancer

Sharudin

Din

Azahar

et al. 2022

Asian Pac J Cancer Prev

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“…VGICs and, in particular, VGSCs have been reported to be expressed and promote invasive abilities and progression in cervical [ 183 , 184 ], ovarian [ 185 , 186 , 187 ], colorectal [ 30 , 188 , 189 , 190 , 191 , 192 ], gastric [ 193 , 194 ] and non-small cell lung cancer (NSCLC) [ 195 , 196 ], as well as in myeloid leukemia [ 197 ] cells.…”

Section: Aeds In Other Tumor Typesmentioning

confidence: 99%

From HDAC to Voltage-Gated Ion Channels: What’s Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer

Pellegrino

Ricci

Ceraldi

et al. 2022

Cancers

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Cancer is a major health burden worldwide. Although the plethora of molecular targets identified in the last decades and the deriving developed treatments, which significantly improved patients’ outcome, the occurrence of resistance to therapies remains the major cause of relapse and mortality. Thus, efforts in identifying new markers to be exploited as molecular targets in cancer therapy are needed. This review will first give a glance on the diagnostic and therapeutic significance of histone deacetylase (HDAC) and voltage gated ion channels (VGICs) in cancer. Nevertheless, HDAC and VGICs have also been reported as molecular targets through which antiepileptic drugs (AEDs) seem to exert their anticancer activity. This should be claimed as a great advantage. Indeed, due to the slowness of drug approval procedures, the attempt to turn to off-label use of already approved medicines would be highly preferable. Therefore, an updated and accurate overview of both preclinical and clinical data of commonly prescribed AEDs (mainly valproic acid, lamotrigine, carbamazepine, phenytoin and gabapentin) in breast, prostate, brain and other cancers will follow. Finally, a glance at the emerging attempt to administer AEDs by means of opportunely designed drug delivery systems (DDSs), so to limit toxicity and improve bioavailability, is also given.

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“…This gene functions as Ca 2+ activated Cl − channels (CaCCs), an ion channel involved in transepithelial ion transport and smooth muscle contraction 33 . Of note, calcium channels play a significant role in controlling cell cycle and resistance to apoptosis 34 . The specific significance of ANO2 relative to OC needs to be investigated.…”

Section: Svmmentioning

confidence: 99%

Precision gynecologic oncology: circulating cell free DNA epigenomic analysis, artificial intelligence and the accurate detection of ovarian cancer

Bahado‐Singh

Ismail

Al-Wahab

et al. 2022

Sci Rep

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Ovarian cancer (OC) is the most lethal gynecologic cancer due primarily to its asymptomatic nature and late stage at diagnosis. The development of non-invasive markers is an urgent priority. We report the accurate detection of epithelial OC using Artificial Intelligence (AI) and genome-wide epigenetic analysis of circulating cell free tumor DNA (cfTDNA). In a prospective study, we performed genome-wide DNA methylation profiling of cytosine (CpG) markers. Both conventional logistic regression and six AI platforms were used for OC detection. Further, we performed Gene Set Enrichment Analysis (GSEA) analysis to elucidate the molecular pathogenesis of OC. A total of 179,238 CpGs were significantly differentially methylated (FDR p-value < 0.05) genome-wide in OC. High OC diagnostic accuracies were achieved. Conventional logistic regression achieved an area under the ROC curve (AUC) [95% CI] 0.99 [± 0.1] with 95% sensitivity and 100% specificity. Multiple AI platforms each achieved high diagnostic accuracies (AUC = 0.99–1.00). For example, for Deep Learning (DL)/AI AUC = 1.00, sensitivity = 100% and 88% specificity. In terms of OC pathogenesis: GSEA analysis identified ‘Adipogenesis’ and ‘retinoblastoma gene in cancer’ as the top perturbed molecular pathway in OC. This finding of epigenomic dysregulation of molecular pathways that have been previously linked to cancer adds biological plausibility to our results.

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Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

Cited by 17 publications

References 198 publications

Invasion and Metastasis Suppression by Anti-Neonatal Nav1.5 Antibodies in Breast Cancer

Invasion and Metastasis Suppression by Anti-Neonatal Nav1.5 Antibodies in Breast Cancer

From HDAC to Voltage-Gated Ion Channels: What’s Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer

Precision gynecologic oncology: circulating cell free DNA epigenomic analysis, artificial intelligence and the accurate detection of ovarian cancer

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