Grant: CIHR New Investigator

The goal to improving mortality from cancer is to achieve complete response to therapy. However, chemotherapy resistance has been a difficult problem to overcome. In order to better understand this phenomenon, our laboratory used a whole genome approach to obtain a snapshot of the changes that occur when cancer cells develop resistance to chemotherapy. This allowed us to identify SPARC as a gene that may play a role in changing the sensitivity of cancer cells to chemotherapy. We have been able to demonstrate that low SPARC levels in chemotherapy resistant human MIP101 colon cancer cells was associated with cancer cells that were resistant to therapy. However, if SPARC was restored by either re-expressing this gene at higher levels, or by introducing the SPARC protein in tissue culture, colon cancer cells became more sensitive to chemotherapy. In animal models, treatment with SPARC also allowed colon cancer cells to respond better to chemotherapy, and this was demonstrated by greater tumor regression in animals receiving SPARC with chemotherapy than in animals receiving chemotherapy alone. These exciting preliminary results serve as the basis of this research grant, as it proposes to study the mechanisms by which SPARC changes the sensitivity of colon cancer cells to chemotherapy. The ultimate goal in understanding these mechanisms is the possibility of developing additional agents that would be useful in the treatment of colon cancer, especially in cases of previously failed cancer therapy.