Metastasis remains the single greatest challenge that breast cancer patients face, because therapeutics directed against metastatic breast cancer result in only partial and transient responses. Immunotherapies that reactivate the patient's immune cells to attack breast cancer cells have the potential to eliminate even large metastatic tumors, but only <20% of patients will respond to current immunotherapies. We have found that the MYC cancer gene is frequently overactivated in aggressive breast cancer and discovered pathways, which when inhibited can preferentially kill MYC high cells, while sparing non-tumor cells - an approach known as synthetic lethality (SL). Such SL and immunotherapy combining approaches are being translated by us and the partners to early-phase clinical studies. In this proposal, we explore MYC and using advanced pre-clinical models, we seek to identify better SL plus immunotherapy combinations which can be translated to next-generation clinical trial concepts.

2022

2026