Transient receptor potential canonical 4 and 5 proteins as targets in cancer therapeutics.
Novel approaches towards cancer therapy are urgently needed. One approach might be to target ion channels mediating Ca2+entry because of the critical roles played by Ca2+in many cell types, including cancer cells. There are several types of these ion channels, but here we address those formed by assembly of transient receptor potential canonical (TRPC) proteins, particularly those which involve two closely related members of the family: TRPC4 and TRPC5. We focus on these proteins because recent studies point to roles in important aspects of cancer: drug resistance, transmission of drug resistance through extracellular vesicles, tumour vascularisation, and evoked cancer cell death by the TRPC4/5 channel activator (-)-englerin A. We conclude that further research is both justified and necessary before these proteins can be considered as strong targets for anti-cancer cell drug discovery programmes. It is nevertheless already apparent that inhibitors of the channels would be unlikely to cause significant adverse effects, but, rather, have other effects which may be beneficial in the context of cancer and chemotherapy, potentially including suppression of innate fear, visceral pain and pathological cardiac remodelling.
School of Medicine, University of Leeds, LIGHT Building, Clarendon Way, Leeds, LS2 9JT, UK. bs10hg@leeds.ac.uk.
Hannah J
HJ
Gaunt
School of Medicine, University of Leeds, LIGHT Building, Clarendon Way, Leeds, LS2 9JT, UK.
Naveen S
NS
Vasudev
School of Medicine, University of Leeds, LIGHT Building, Clarendon Way, Leeds, LS2 9JT, UK. d.j.beech@leeds.ac.uk.
David J
DJ
Beech
D000818:Animals; D019008:Drug Resistance, Neoplasm; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D050052:TRPC Cation Channels / Q000378:metabolism*
D050052:TRPC Cation Channels; C489571:TRPC4 ion channel
Breast cancer; Calcium ion; Cancer cell; Englerin A; Ewing’s sarcoma; Ion channel; Non-selective cationic channel; Renal cell carcinoma; Transient receptor potential canonical