Grant: Project Grant

Targeting tumor-specific molecular alterations is crucial for optimizing cancer treatment and finding new targets is essential for the development of novel, more efficient therapeutic approaches. Previous work has implicated a cell surface molecule called EphA2 in enhancing aggressiveness of multiple malignancies, including breast cancer. In fact, EphA2 is overexpressed in the majority of breast tumors. We recently found that human triple-negative breast cancer (TNBC) tumors could be suppressed in mouse models by targeting EphA2 with a synthetic anti-EphA2 antibody. However, a small percentage of tumor cells remain resistant to this treatment. To improve tumor elimination, we plan to use a novel approach called "Synthetic Lethality" (SL), where an inhibition of a SL gene selectively kills resistant cancer cells. Identification and validation of these SL genes would trigger the development of new efficient combination therapies, co-targeting EphA2 and SL genes, which is expected to eradicate TNBC tumors. This is important, as currently there is no effective therapy for TNBC and it is associated with a high rate of patient mortality. In addition, we will use our anti-EphA2 antibody for developing tumor-imaging reagents that would allow to apply non-invasive procedures to identify patients expressing EphA2 in their tumors, who are most likely to benefit from anti-EphA2 treatment. This will help to personalize anti-EphA2 TNBC therapy based on EphA2 expression profiles and thus, optimize its clinical application. Overall, our work will to help to develop new personalized combination therapies that should significantly improve survival of patients affected by TNBC.