Efficacy of an EGFR-Specific Peptide against EGFR-Dependent Cancer Cell Lines and Tumor Xenografts

摘要: We have recently synthesized a peptide called Disruptin, which comprised the SVDNPHVC segment of epidermal growth factor receptor (EGFR) that inhibits binding heat shock protein 90 (Hsp90) to EGFR and EGF-dependent dimerization cause degradation. The effect is specific for versus other Hsp90 client proteins [Ahsan et al.: (2013). Destabilization by dimerization. J Biol Chem288, 26879-26886]. Here, we show Disruptin decreases clonogenicity variety EGFR-dependent cancer cells in culture but not EGFR-independent or noncancerous cells. selectivity toward EGFR-driven due high level EGF stimulation tumor relative normal When administered intraperitoneal injection into nude mice bearing human xenografts, causes extensive degradation adjacent host tissue. markedly tumors without producing major toxicities caused inhibitor geldanamycin cisplatin. These findings provide proof concept development new Disruptin-like class antitumor drugs are directed specifically against tumors.