“Two decades ago a class of ion channels, hitherto unsuspected, was discovered. In mammals these Transient Receptor Potential channels (TRPs) have not only expanded in number (to 26 functional channels) but also expanded the view of our interface with the physical and chemical environment,” explained the study authors, whose work was published in the Journal of Cancer. The researchers added, “Many TRP channels are major players in nociception and integration of pain signals. One member of the vanilloid sub-family of channels is TRPV6. This channel is highly selective for divalent cations, particularly calcium, and plays a part in general whole-body calcium homeostasis, capturing calcium in the gut from the diet. TRPV6 can be greatly elevated in a number of cancers deriving from epithelia and considerable study has been made of its role in the cancer phenotype where calcium control is dysfunctional.”
SOR-C13 is a selective TRPV6 inhibitor and is the first to undergo clinical trial observation and is currently being assessed at MD Anderson Cancer Center. According to a press release, “SOR-C13 binds with high affinity and selectivity and disrupts the function of TRPV6. TRPV6 plays a central role in a biochemical cascade that results in the upregulation of an array of pro-cancerous genes and is considered to be an important target for novel anticancer therapy.”
In a summary of their research findings, the study authors wrote that previous research observed good outcomes for TRPV6 inhibition in animal models, and more recent findings suggest its efficacy in humans, too. Looking ahead, they said, “The key issues to be resolved for a successful antagonist of TRPV6 are: an IC50 low enough to be clinically meaningful (i.e., required dose), specificity in inhibiting only TRPV6, low human toxicity, bio-stability, and cost. Still, it is unclear how the expression of TRPV6 gene and production of protein is up regulated in these cancers and that may offer another route to exploit TRPV6.”
SOR-C13 was developed by Soricimed.
“TRPV6 has been discussed in the literature as a target for cancer therapy for nearly 20 years,” said corresponding study author professor Jack Stewart, co-founder and chief scientific officer of Soricimed, in a press release. “This article compiles everything we know about TRPV6 – how it works, its mechanism of action as an oncochannel and what controls its gene expression. In addition to demonstrating TRPV6 as a useful target for solid cancers, this publication outlines how we can exploit TRPV6’s overexpression to treat several cancer types.”