Targeting tumors with TRPV6
MONCTON, New Brunswick—Soricimed Biopharma Inc., a clinical-stage pharmaceutical company discovering and developing targeted cancer therapeutics and diagnostics, has announced the peer-reviewed publication of new results from its anticancer research program in the Journal of Cancer. The privately held Canadian company, which is funded through private investors and various programs from the governments of Canada and New Brunswick, asserts that its drug candidates have demonstrated a capability to reduce cancer cell viability, induce apoptosis and to reduce human tumor volume while minimizing side effects in classic animal and in-vitro tumor models.
The journal article, “Inhibition of Transient Receptor Potential Vanilloid 6 Channel (TRPV6), Elevated in Human Ovarian Cancers, Reduces Tumor Growth in a Xenograft Model,” provides further support for the importance of TRPV6 in ovarian cancer. This calcium channel is the target for Soricimed’s anticancer drug candidates, and in the paper, the company demonstrates that the genetic message (mRNA) for TRPV6 protein and TRPV6 protein itself are greatly elevated in biopsies of all five types of ovarian cancer, at all stages. This is consistent with what has been reported for other solid tumor cancers, such as in the prostate or breast.
“We also show targeting TRPV6 with our lead drug candidate SOR-C13 inhibits ovarian tumor growth in animal models,” said corresponding author Prof. Jack Stewart, co-founder and chief scientific officer of Soricimed. “The conclusion from this work is that TRPV6 is a relevant therapeutic target for this difficult to treat disease.”
He added, “The role of TRPV6 in prostate and breast cancers is well documented, since it was first noted in 2002. TRPV6’s role in ovarian cancers that we report in this publication hadn’t been studied extensively until now. It is difficult to introduce a new cancer target to the oncology community but, in this case, the weight of evidence makes it quite clear that TRPV6 plays a key role in cancer pathogenesis. In addition, new data coming out indicates that ductal pancreatic cancer has also joined the TRPV6-rich cancer group.”
Soricimed also announced positive results demonstrating safety, tolerability and potential activity in a multicenter Phase 1 trial of SOR-C13 in patients who had advanced solid tumor cancers. SOR-C13 has been granted orphan drug status by the U.S. Food and Drug Administration for treatment of ovarian and pancreatic cancer.
Stewart discovered that the Morthern short-tailed shrew is the only known mammal in North America that secretes a paralytic venom. After the discovery, he and his colleagues were the first to purify, characterize and synthesize this paralytic toxin, a unique peptide that inhibits sodium channels in nerves and offers potential for non-opioid pain treatment. Stewart named this protein soricidin, and Soricimed Biopharma was born.
Further research on soricidin brought Stewart and his colleagues to the identification of two unique biological functions within the peptide—one domain that is paralytic and a second domain that is anticancerous. Soricimed discovered that the target of the anticancer activity of soricidin was the calcium ion channel known as TRPV6. Solid tumor cancers produce large amounts of this channel. Because it plays a major role in cancer cell growth, proliferation and metastases, the channel represents a compelling target for the development of new cancer treatments. Additional characterization of the anti-cancer domain of soricidin culminated in the identification of a subset of small peptides that are highly selective inhibitors of TRPV6 and candidates for development as anticancer therapeutics.
TRPV6, one of approximately 33 ion channels in the super-family of TRP channels, is selective for calcium ion and is constitutively active. Its major function is uptake of calcium into the body through the gut. TRPV6 is now recognized as an oncochannel and its gene classified as an oncogene or proto-oncogene, according to Stewart.
High expression of TRPV6 in breast cancer is consistent with pathological parameters and poor patient outcomes. Elevated TRPV6 has also been reported in estrogen receptor-negative breast cancers and correlated with poor prognosis for patients. All five types of ovarian cancer show similar elevated levels of both TRPV6 mRNA and protein. Over-expression of TRPV6 results in sustained elevation of calcium within the cancer cell, leading to cell proliferation and metastasis and inhibition of programmed cell death.
Stewart summarized, “Soricimed is the first company to develop a specific inhibitor of TRPV6 and to take it into clinical development as a potential treatment for solid-tumor cancers. Although the precise details of the TRPV6 pathway in cancer remain to be fully elucidated, a viable model now exists and is based on increased intracellular calcium resulting from the over-expression of TRPV6.”