Grant: Operating Grant

According to the Canadian Cancer Society, 40% of Canadian women and 45% of men will develop cancer during their lifetimes, and 1 out of every 4 Canadians will die of cancer. A major problem that increases mortality is the spread of cancer cells from the primary tumor site to other organs and tissues in a process known as metastasis. Recently two closely related compounds named neopetrosiamide A and B were isolated from a sponge off Papua New Guinea and shown to convert metastatic cells to a seemingly normal state and prevent their invasion of human tissues. Our group recently revised the chemical structures assigned to neopetrosiamides and made them in the laboratory together with few active analogs. As collection of sponge cannot supply the amounts of neopetrosiamides needed for biological studies or clinical use, we propose to develop synthetic methods to make improved analogs and simpler, more accessible, derivatives. In addition, we propose to make derivatives bearing handles for attachment of fluorescent labels and to use these to study the mechanism of action of such potential drugs on metastatic tumor cells. The results will provide significant amounts of this drug candidate for study and will allow its assessment as a possible therapeutic agent. It should also reveal new cellular targets to prevent invasion of healthy tissue by tumor cells.