Grant: Master's Award: Canada Graduate Scholarships

Cancer metastasis is a process by which cancer cells spread from primary tumors to other tissues is responsible for 90% of cancer related deaths. These high mortality rates speak to the urgent need to improve therapies that prevent metastasis. Metastatic cancer cells rely on the actin cytoskeleton to form specialized structures that allow them to move and break through tissue barriers, and these structures can be targeted with actin toxins. Mycalolide B (MycB) is an actin toxin that our lab has identified as a potent inhibitor of metastatic cancer cells. To build towards clinical application, we plan to build a new class of antibody-drug conjugates (ADC's) by linking synthetic analogs of MycB to clinical grade oncology antibodies to allow specific release of the toxins in tumor cells. This new class of ADCs will complement current ADC's that primarily target rapidly dividing cells by delivering microtubule toxins. Since supply is limited for MycB, we have collaborated with medicinal chemists at Queen's to build a panel of synthetic analogs. My project involves the ranking of these analogs for disruption of the actin cytoskeleton in metastatic cancer cells. Given our promising results, we have established a collaboration with an industry partner to make novel actin toxin ADCs for testing in mouse models of human metastatic cancer. These novel ADCs will allow for specific delivery of a potent actin toxin to tumor cells, and either as a single therapy or in combination with existing therapies will reduce metastasis and improve survival rates.