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Oncology

A major challenge to modern medicine is the diagnosis and treatment of cancers.  Development of new insights into the biology of cancer have provided new strategies for the management of these diseases. It has become clear over the last number of years that the various signaling pathways cells used to communicate internally and externally are often compromised or hijacked. A common factor in a number of cancers developing in epithelial tissues such as ovarian, prostate and breast cancer is the presence of dysfunctional signaling triggered by calcium entry into the cell.

 
The key factor in disruptive entry of too much calcium into cancer cells is the overproduction of a calcium ion channel that is not present, or present at low levels, in healthy tissues. The calcium channel that has come to light as a major player is TRPV6 (Transient Receptor Potential, Vanilloid family, number 6). Ovarian, breast and prostate cancers (among others) produce very large amounts of this channel and the flood of calcium into the cell appears to initiate cell growth, proliferation and metastases.  The flood of calcium promotes a pathway that stops the self-destruct sequence (apoptosis), present in all cells, but triggered by damaged or stressed cells.
 
Our C-series peptides selectively and powerfully stop the TRPV6 channels from working and reset the cell toward normal calcium content. As such, the C-series peptides are first-in-class with this activity and act through a physiological rather than cytotoxic mechanism. As the calcium content decreases, the inhibition of the self-destruct pathway (apoptosis) is lifted and the cells die. While the involvement of the TRPV6 channel in tumour growth and metastasis has been recognized for about a 15 years, our C-series peptides are the only known inhibitors that are compatible with medical application. The very low toxicity profile of our C-series peptides and lack of side effects is a powerful incentive for us to develop this class of compounds.
 
The oncology platform we have developed from soricidin, gives us the first viable inhibitor of the TRPV6 calcium channel. Inhibition of TRPV6 that is over-expressed in ovarian cancers initiates apoptosis in human tumour xenografts and shrinks tumours with a very low toxicity profile.
With the successful studies in many cancer cell lines and xenograft work in mice, and with completion of pre-clinical GLP toxicology work, we are in a Phase I clinical trial to underscore the safety and potential early utility of these peptides. The Phase I human trial is a multicenter, open-label, dose escalation study taking place at cancer centres in both the United States and Canada with results expected in 2015.