Format

Send to

Choose Destination
Neoplasia. 2014 Feb;16(2):105-14. doi: 10.1593/neo.14182.

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

Author information

1
Department of Radiation Oncology, The University of Michigan Medical School, Ann Arbor, MI.
2
Unit for Laboratory Animal Medicine, The University of Michigan Medical School, Ann Arbor, MI.
3
Department of Biostatistics, The University of Michigan Medical School, Ann Arbor, MI.
4
Department of Radiology, The University of Michigan Medical School, Ann Arbor, MI.
5
Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, MI.
6
Department of Radiation Oncology, The University of Michigan Medical School, Ann Arbor, MI. Electronic address: nyati@umich.edu.

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.

PMID:
24709418
PMCID:
PMC3978391
DOI:
10.1593/neo.14182
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center