Projects

Hereditary mutations in cancer predisposing genes and aging are two of the major risk factors for cancer. Thus, studying differences in normal tissues associated with germline mutation and with age will help elucidate factors driving the earliest stages of tumor progression, which can then be used as targets for cancer prevention. They have identified Mdk (midkine) as a gene upregulated with age. Higher MDK in normal breast tissue is associated with higher cancer risk in younger women. MDK treatment of young rats mimicked age-related changes and promoted mammary tumorigenesis. They have also identified Mdk as a regulator of age-related luminal progenitors, the cells that serve as cell-of-origin of mammary tumors. Based on these data, they hypothesize that targeting mammary epithelial progenitors and MDK signaling can prevent breast cancer in high-risk women. The goals of this proposal are to test whether breast cancer can be prevented by decreasing the numbers of progenitors that are present in early proliferative premalignant lesions using a vaccine that targets these cells and inhibition of MDK signaling.