Grant: Project Grant - PA: Breast Cancer Research

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 cell surface molecules called EGFR and EphA2 in enhancing aggressiveness of multiple malignancies, including breast cancer. In fact, EGFR and EphA2 are very often overexpressed in breast tumors. We recently found that human triple negative breast cancer (TNBC) tumors could be suppressed by co-targeting EGFR and EphA2 with a bispecific anti-EGFR/EphA2 antibody in animal models. However, a small percentage of tumor cells remain resistant to this treatment. To overcome this, we plan to use a completely unbiased integrative strategy based on the analyses of genomes and signaling proteins in resistant tumor cell populations to identify "rescue" genes that can be targeted to selectively kill resistant TNBC cells. Identification of these rescue genes would trigger the development of therapies based on their inhibition combined with anti-EGFR/EphA2 application, which should further improve elimination of TNBC tumors. As an alternative approach, we will generate anti-EGFR/EphA2 radioconjugates, as these compounds are also expected to assure very effective tumor eradication in patients with triple negative breast cancer. This is important, as currently there is no effective therapy for TNBC and it is associated with a high rate of patient mortality.