Detecting and Targeting Oncogenic Myc in Breast Cancer
Annual rept. 10 May 2004-9 May 2005
UNIVERSITY HEALTH NETWORK TORONTO (ONTARIO) GRANT AND CONTRACT SERVICES
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Deregulation of the cellular myc proto-oncogene is one of the strongest activators of tumorigenesis and understanding the target genes and pathways regulated by this transcription factor in cancer etiology will clearly mark a key advance. Myc expression and activity are highly restricted in normal human mammary epithelial cells HMECs, but unleashed and deregulated in cells of malignant transformations. Because the protein product is identical in normal and tumor cells, three major issues arise. First, a definitive approach to detect oncogenic Myc in primary tumor specimens is severely lacking and long overdue. This issue has plagued the field during the two decades since Myc was first discovered. Second, it remains unclear whether Myc function is different in normal and tumor cells. Myc may regulate the same subset of target genes in both settings, but in a more robust manner in tumor cells. By contrast, deregulated, overexpressed Myc protein may bind and regulate an additional unique set of target genes in tumor cells. This issue has not yet been explored. Third, although it is clear that inhibiting Myc can trigger tumor regression and eradication in animal models, few initiatives are underway to target Myc as a therapeutic approach for human disease. Because Myc protein in normal and tumor cells is indistinguishable, it is thought that anti-Myc inhibitors would have little to no tumor specificity or therapeutic index. Clearly a novel approach is required.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology