Grant: Project Grant

Breast cancer is the most diagnosed malignancy in women and is second only to lung cancer in cancer-related deaths. Once breast cancers have spread to other parts of the body, the 5-year survival rate is <30% and current standard of care therapies remain palliative in the metastatic setting. There is an urgent need to identify more effective therapeutic strategies to either prevent the development of breast cancer metastasis in women who present with advanced disease or to shrink established visceral metastases where surgery is no longer an option. Breast cancers can be stratified based into distinct subtypes, including HER2+ and triple-negative breast cancer (TNBC), which are associated with poor survival outcomes, owing in part to their propensity to metastasize compared to other breast cancer subtypes. This multidisciplinary team developed a novel therapeutic compound (called MG-002) which blocks the ability of breast cancer cells to synthesize proteins and generated compelling data that it selectively and potently kills metastatic breast cancer cells. MG-002 significantly prevents the development of lung metastases and reduces the lung and liver metastatic burden in animals with established metastases. In this grant, we will 1) understand the molecular mechanism underlying the anti-metastatic functions of MG-002, 2) characterize the anti-tumor immune responses induced by MG-002, and 3) identify druggable targets to develop combination strategies to enhance anti-metastatic efficacy of MG-002. This research has the potential to overcome the significant hurdles of tumor heterogeneity, which have impeded the development of targeted therapies to treat metastatic breast cancers, by informing rational combination therapies to treat a larger percentage of women diagnosed with this disease, improving patient survival.