Abstract
Ion transporting proteins (ITPs) comprise a wide range of ion channels, exchangers, pumps and ionotropic receptors many of which are expressed in tumours and contribute dynamically to the different components and stages of the complex cancer process, from initiation to metastasis. In this promising major field of biomedical research, several candidate ITPs have emerged as clinically viable. Here, we consider a series of general issues concerning the oncological potential of ITPs focusing on voltage-gated sodium channels as a ‘case study’. First, we outline some key properties of ‘cancer’ as a whole. These include epigenetics, stemness, metastasis, heterogeneity, neuronal characteristics and bioelectricity. Cancer specificity of ITP expression is evaluated in relation to tissue restriction, splice variance, functional specificity and macro-molecular complexing. As regards clinical potential, diagnostics is covered with emphasis on enabling early detection. For therapeutics, we deal with molecular approaches, drug repurposing and combinations. Importantly, we emphasise the need for carefully designed clinical trials. We highlight also the area of ‘social responsibility’ and the need to involve the public (cancer patients and healthy individuals) in the work of cancer research professionals as well as clinicians. In advising patients how best to manage cancer, and live with it, we offer the following four principles: Awareness and prevention, early detection, specialist, integrated care, and psychological support. Finally, we highlight four key prerequisites for commercialisation of ITP-based technologies against cancer. We conclude that ITPs offer significant potential as regards both understanding the intricacies of the complex process of cancer and for developing much needed novel therapies.
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Abbreviations
- cfDNA:
-
Cell-free DNA
- ctDNA:
-
Circulating tumour DNA
- EGF:
-
Epidermal growth factor
- EMT:
-
Epithelial-mesenchymal transition
- HIF:
-
Hypoxia-inducible factor
- IC:
-
Immune cell
- ITP:
-
Ion transporting protein
- KCa:
-
Calcium-activated potassium channel
- lncRNA:
-
Long, noncoding RNA
- miRNA:
-
microRNA
- NCX:
-
Sodium-calcium exchanger
- NE:
-
Neural element
- NHE:
-
Sodium-hydrogen exchanger
- NRSF:
-
Neuron restrictive silencer factor
- NSCLC:
-
Non-small-cell lung cancer
- PKA:
-
Protein kinase A
- REST:
-
RE1-silencing transcription factor
- siRNA:
-
Small interfering RNA
- TME:
-
Tumour micro-environment
- TTX:
-
Tetrodotoxin
- VGIC:
-
Voltage-gated ion channel
- VGSC:
-
Voltage-gated sodium channel
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Acknowledgements
Our research has been supported over many years by numerous granting agencies and first-class research students and associates (too many to list individually). We are particularly indebted to the Trustees of the Pro Cancer Research Fund (PCRF) for unfailing support of some 20 years.
Conflict of Interest Statement
MBAD is involved in a small biotech company aiming broadly to realise the clinical potential of VGSC expression in cancer.
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Djamgoz, M.B.A. (2021). Ion Transporting Proteins and Cancer: Progress and Perspectives. In: Stock, C., Pardo, L.A. (eds) Targets of Cancer Diagnosis and Treatment. Reviews of Physiology, Biochemistry and Pharmacology, vol 183. Springer, Cham. https://doi.org/10.1007/112_2021_66
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