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Efficacy of an EGFR-specific peptide against EGFR-dependent cancer cell lines and tumor xenografts.


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

SUBMITTER: Ahsan A 

PROVIDER: S-EPMC3978391 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Efficacy of an EGFR-specific peptide against EGFR-dependent cancer cell lines and tumor xenografts.

Ahsan Aarif A   Ramanand Susmita G SG   Bergin Ingrid L IL   Zhao Lilli L   Whitehead Christopher E CE   Rehemtulla Alnawaz A   Ray Dipankar D   Pratt William B WB   Lawrence Theodore S TS   Nyati Mukesh K MK  

Neoplasia (New York, N.Y.) 20140201 2


We have recently synthesized a peptide called Disruptin, which comprised the SVDNPHVC segment of the epidermal growth factor receptor (EGFR) that inhibits binding of heat shock protein 90 (Hsp90) to the EGFR and EGF-dependent EGFR dimerization to cause EGFR degradation. The effect is specific for EGFR versus other Hsp90 client proteins [Ahsan et al.: (2013). Destabilization of the epidermal growth factor receptor (EGFR) by a peptide that inhibits EGFR binding to heat shock protein 90 and recepto  ...[more]

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