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Published on: April 22, 2019
Pan-HER Inhibitor Augments Radiation Response in Human Lung and Head and Neck Cancer Models
David M Francis1, Shyhmin Huang1, Eric A Armstrong1
1Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
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.
Insights
Pan-HER, a novel therapy targeting the EGF receptor family, enhances radiation effectiveness in lung and head and neck cancers. This combination therapy shows potent antitumor effects and supports further clinical investigation.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Aberrant signaling of the Epidermal Growth Factor Receptor (EGFR) family (EGFR, HER2, HER3, HER4) is implicated in epithelial cancer development and spread.
- Pan-HER is a novel therapeutic agent comprising six monoclonal antibodies targeting EGFR, HER2, and HER3.
Purpose of the Study:
- To evaluate Pan-HER's efficacy in enhancing radiation response in lung and head and neck cancers.
- To assess Pan-HER's effectiveness in EGFR inhibitor-resistant models.
Main Methods:
- Testing Pan-HER's antiproliferative and radiosensitizing effects in human cancer cell lines and xenografts.
- Investigating the molecular mechanisms of Pan-HER's action, including DNA repair, apoptosis, cell cycle, and senescence.
- Evaluating combined Pan-HER and radiation treatment in human tumor xenografts.
Main Results:
- Pan-HER exhibited superior antiproliferative and radiosensitizing effects compared to cetuximab.
- Mechanisms include impaired DNA damage repair, increased programmed cell death, cell cycle redistribution, and induced senescence.
- Combined Pan-HER and radiation therapy demonstrated significant antitumor activity and prolonged regrowth delay in xenografts.
Conclusions:
- Pan-HER effectively enhances radiation response in preclinical models of lung and head and neck cancers.
- The combination of Pan-HER with radiation presents a promising strategy for clinical development.
- Further investigation into Pan-HER and radiation therapy is warranted for these cancer types.
