Triple negative breast cancer (TNBC) is the only major type of breast cancer for which no specific FDA approved target therapy is available to improve patient outcomes. TNBC lacks the usual targets estrogen receptor (ER), Progesterone receptor (PR) and HER2/neu receptor. Recently, the epidermal growth factor receptor (EGFR) has emerged as one of the potential targets in TNBC.  Epidermal growth factor (EGF) mediates several cellular functions and processes such as survival, motility, differentiation, proliferation, and death.  When it is released by epidermal tissues, EGF binds to cell surface receptors such as the Epidermal growth factor receptor (EGFR) causing its dimerization.  Receptor dimerization activate the tyrosine kinase activity of the cytoplamic domain of the receptor which then causes a signal transduction that leads DNA synthesis and cell proliferation.  Apart from EGF, EGFR is reported to bind to Transforming growth factor alpha (TGF-α), Argos and Potato Carboxypeptidase inhibitor (PCI). All of these small proteins have unique disulfide bridges (knots) that presents a unique binding motif and are able to compete with EGF thereby antagonizing its action. We have used an integrated proteomics assisted computational drug discovery approach to generate several peptidomimetics and small molecules targeting EGF-EGFR protein-protein interactions. We believe these inhibitors can be used as tools to understand the role of EGFR in TNBC and provide clues towards novel therapeutics to combat TNBC.

Epidermal growth factor receptor (EGFR) inhibitors as novel anti-cancer agents to combat triple-negative breast cancer

251st National Meeting (2016)

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