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Clin Cancer Res. 2016 Feb 1;22(3):633-43. doi: 10.1158/1078-0432.CCR-15-1664. Epub 2015 Sep 29.

Pan-HER Inhibitor Augments Radiation Response in Human Lung and Head and Neck Cancer Models.

Author information

1
Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
2
Symphogen A/S, Ballerup, Denmark.
3
Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. harari@humonc.wisc.edu.

Abstract

PURPOSE:

Aberrant regulation of the EGF receptor family (EGFR, HER2, HER3, HER4) contributes to tumorigenesis and metastasis in epithelial cancers. Pan-HER represents a novel molecular targeted therapeutic composed of a mixture of six monoclonal antibodies against EGFR, HER2, and HER3.

EXPERIMENTAL DESIGN:

In the current study, we examine the capacity of Pan-HER to augment radiation response across a series of human lung and head and neck cancers, including EGFR inhibitor-resistant cell lines and xenografts.

RESULTS:

Pan-HER demonstrates superior antiproliferative and radiosensitizing impact when compared with cetuximab. The mechanisms underlying these effects appear to involve attenuation of DNA damage repair, enhancement of programmed cell death, cell-cycle redistribution, and induction of cellular senescence. Combined treatment of Pan-HER with single or fractionated radiation in human tumor xenografts reveals a potent antitumor and regrowth delay impact compared with Pan-HER or radiation treatment alone.

CONCLUSIONS:

These data highlight the capacity of Pan-HER to augment radiation response in lung and head and neck cancer models and support investigation of Pan-HER combined with radiation as a promising clinical therapeutic strategy.

PMID:
26420857
DOI:
10.1158/1078-0432.CCR-15-1664
[Indexed for MEDLINE]
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