@article{dafa66f362704459bf954da5336109d1,
title = "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 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.",
author = "Aarif Ahsa and Ramanand, {Susmita G.} and Bergin, {Ingrid L.} and Lilli Zha and Whitehead, {Christopher E.} and Alnawaz Rehemtulla and Dipankar Ray and Pratt, {William B.} and Lawrence, {Theodore S.} and Nyati, {Mukesh K.}",
note = "Funding Information: Address all correspondence to: Mukesh K. Nyati or Theodore S. Lawrence, Department of Radiation Oncology, The University of Michigan Medical School, Medical Science Building I, Ann Arbor, MI 48109-2026. E-mail: nyati@umich.edu 1This work was supported by National Institutes of Health grants R01 CA131290 (to M.K.N.), R01 CA160981 (to D.R.), P50 CA097248 [to Principal Investigator (PI): Wolf, Co-Investigator Project 4 to M.K.N.], P50 CA097248 (to PI: Wolf, Career Development Award under P50 CA097248 to A.A.), and a Cancer Center support grant P30 CA46592. Support was also received from the Michigan Institute for Clinical and Health Research (to M.K.N.), the James Stuart and Barbara Padnos Funds for Cancer Research (to M.K.N.), and an Alfred Taubman Scholarship (to T.S.L.). This project is a component of the University of Michigan Medical School{\textquoteright}s Fast Forward Strategic Research Initiative. Disclosure of potential conflicts of interest: Provisional Application entitled “Inhibitors of the Epidermal Growth Factor Receptor-Heat Shock Protein 90 Binding Interaction,” filed on 20 December 2010. 2This article refers to supplementary materials, which are designated by Tables W1 and W2 and Figures W1 to W3 and are available online at www.neoplasia.com. 3A.A and S.G.R. contributed equally to this work. Received 23 January 2014; Revised 23 January 2014; Accepted 23 January 2014 Copyright {\textcopyright} 2014 Neoplasia Press, Inc. All rights reserved 1522-8002/14/$25.00 DOI 10.1593/neo.14182",
year = "2014",
month = feb,
doi = "10.1593/neo.14182",
language = "English (US)",
volume = "16",
pages = "105--114",
journal = "Neoplasia (United States)",
issn = "1522-8002",
publisher = "Elsevier Inc.",
number = "2",
}