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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 2/2009

Open Access 01-01-2009 | Original Article

Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors

Authors: Matthew E. Hardee, Rose J. Eapen, Zahid N. Rabbani, Matthew R. Dreher, Jeffrey Marks, Kimberly L. Blackwell, Mark W. Dewhirst

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2009

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Abstract

Purpose

Tumor hypoxia reduces the efficacy of radiation and chemotherapy as well as altering gene expression that promotes cell survival and metastasis. The growth factor receptor, Her2/neu, is overexpressed in 25–30% of breast tumors. Tumors that are Her2+ may have an altered state of oxygenation, relative to Her2− tumors, due to differences in tumor growth rate and angiogenesis.

Methods

Her2 blockade was accomplished using an antibody to the receptor (trastuzumab; Herceptin). This study examined the effects of Her2 blockade on tumor angiogenesis, vascular architecture, and hypoxia in Her2+ and Her2− MCF7 xenograft tumors.

Results

Treatment with trastuzumab in Her2+ tumors significantly improved tumor oxygenation, increased microvessel density, and improved vascular architecture compared with the control-treated Her2+ tumors. The Her2+ xenografts treated with trastuzumab also demonstrated decreased proliferation indices when compared with control-treated xenografts. These results indicate that Her2 blockade can improve tumor oxygenation by decreasing oxygen consumption (reducing tumor cell proliferation and inducing necrosis) and increasing oxygen delivery (vascular density and architecture).

Conclusions

These results support the use of trastuzumab as an adjunct in the treatment of breast tumors with chemotherapy or radiotherapy, as improvements in tumor oxygenation should translate into improved treatment response.
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Metadata
Title
Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors
Authors
Matthew E. Hardee
Rose J. Eapen
Zahid N. Rabbani
Matthew R. Dreher
Jeffrey Marks
Kimberly L. Blackwell
Mark W. Dewhirst
Publication date
01-01-2009
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 2/2009
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-008-0729-3

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