Executive Summary : | Triple negative breast cancer (TNBC) is a aggressive, heterogeneous subtype of cancer that accounts for 15-20% of all breast carcinomas. Its poor prognosis, high relapse rates, and short survival rate necessitate immediate attention to its management. Epithelial cell adhesion molecule (EpCAM) and Epidermal growth factor receptor (EGFR) are key transmembrane proteins with high expression levels in TNBC cells. Targeting moieties with specific binding interactions with these proteins are attractive for drug delivery and breast cancer management. Antibody drug conjugates (ADC) are emerging as next-generation therapeutics for cancer management, offering specificity and potency of cytotoxic drugs to invade cancer cells. Three FDA-approved ADCs are for metastatic breast cancer, indicating potential for targeted drug delivery. However, antibodies have limitations such as engineering time, cost, immunogenicity, and low tissue penetration. This proposal aims to develop short peptides derived from structural understanding of antibody interactions with EGFR and EpCAM using an in-silico tool. These peptides offer advantages such as low cost, ease of synthetic tunability, high tissue penetration, and lack of immunogenicity over antibody-based therapy. Engaging these targets could address challenges associated with TNBC, such as multi-drug resistance and metastasis, and improve the anti-cancer activity of the drug alone. |