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

Aarif Ahsa, Susmita G. Ramanand, Ingrid L. Bergin, Lilli Zha, Christopher E. Whitehead, Alnawaz Rehemtulla, Dipankar Ray, William B. Pratt, Theodore S. Lawrence, Mukesh K. Nyati

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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 EGFdependent 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 Chem 288, 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.

Original languageEnglish (US)
Pages (from-to)105-114
Number of pages10
JournalNeoplasia (United States)
Volume16
Issue number2
DOIs
StatePublished - Feb 2014
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research

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