In metastatic breast cancer, the Epidermal Growth Factor Receptor family of transmembrane tyrosine kinases (ErbB) drives proliferation and metastasis. EGFR, HER2 and ErbB3 are known to be highly expressed and active in both the HER2+ and Triple Negative/Basal subtypes of breast cancer, and have been targeted with varying effectiveness. Importantly, targeting of a single receptor member typically results in activity in the remaining receptor members, making simultaneous targeting of all receptors a needed therapeutic development. Furthermore, while the tyrosine kinase domain of these receptors is a significant driver of transformation, kinase inhibitors fail to induce cell death, indicating that a non-kinase function of the ErbB receptors is important in driving cancer progression. While the tyrosine kinase activity of these receptors is well known, less appreciated are the non-canonical activities of this family, including the modulation of mitochondrial function, calcium signaling and nuclear translocation and activity as transcriptional co-factors. We have discovered and developed peptide therapeutics that disrupt ErbB dynamics effective against metastatic breast cancer as well as glioblastoma. Both in vitro and in vivo data demonstrate the efficacy of these 'first in class' drugs.