Despite the available treatments breast cancer ranks second as the cause of death from cancer in women primarily due to metastases of the primary tumor to other sites in the body. We will extend our preliminary study of the anticancer activity of recombinant human galectin-3 N-terminally truncated by collagenase in an orthotopic mouse model of metastatic breast cancer. We postulate that galectin-3 truncated by collagenase blocks the binding sites for galectin-3 and prevent its cell crosslinking and other activities. We will determine the in vivo efficacy of an analogous galectin-3 variant (delta 107) produced in E. coli and compare it with that of galectin-3 truncated enzymatically. We will perform a dose-response analysis to firmly establish the activity of the delta 107 variant, and address the optimal dose. We will also test the anticancer activity of a slightly longer mutant of galectin-3. A series of cell-based assays would be used to compare the in vitro activities of the galectin-3 variants with intact galectin-3. Further development of truncated galectin-3 as a clinical candidate for breast cancer would be the focus of the Phase II research.
An estimated 40,800 Americans are expected to die of breast cancer this year. A therapy that primarily acts to reduce metastasis could be effective in treating breast cancer, especially early stage cancer. If galectin-3 has a reduced incidence of side effects this would increase its attractiveness. The commercial potential of breast cancer therapeutics is large.
