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

Publication ,  Journal Article
Hardee, ME; Eapen, RJ; Rabbani, ZN; Dreher, MR; Marks, J; Blackwell, KL; Dewhirst, MW
Published in: Cancer Chemother Pharmacol
January 2009

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.

Duke Scholars

Published In

Cancer Chemother Pharmacol

DOI

EISSN

1432-0843

Publication Date

January 2009

Volume

63

Issue

2

Start / End Page

219 / 228

Location

Germany

Related Subject Headings

  • Trastuzumab
  • Transfection
  • Signal Transduction
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Oxygen Consumption
  • Oncology & Carcinogenesis
  • Neovascularization, Pathologic
  • Neoplasm Transplantation
  • Mice, Nude
 

Citation

APA
Chicago
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MLA
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Hardee, M. E., Eapen, R. J., Rabbani, Z. N., Dreher, M. R., Marks, J., Blackwell, K. L., & Dewhirst, M. W. (2009). Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors. Cancer Chemother Pharmacol, 63(2), 219–228. https://doi.org/10.1007/s00280-008-0729-3
Hardee, Matthew E., Rose J. Eapen, Zahid N. Rabbani, Matthew R. Dreher, Jeffrey Marks, Kimberly L. Blackwell, and Mark W. Dewhirst. “Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors.Cancer Chemother Pharmacol 63, no. 2 (January 2009): 219–28. https://doi.org/10.1007/s00280-008-0729-3.
Hardee ME, Eapen RJ, Rabbani ZN, Dreher MR, Marks J, Blackwell KL, et al. Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors. Cancer Chemother Pharmacol. 2009 Jan;63(2):219–28.
Hardee, Matthew E., et al. “Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors.Cancer Chemother Pharmacol, vol. 63, no. 2, Jan. 2009, pp. 219–28. Pubmed, doi:10.1007/s00280-008-0729-3.
Hardee ME, Eapen RJ, Rabbani ZN, Dreher MR, Marks J, Blackwell KL, Dewhirst MW. Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors. Cancer Chemother Pharmacol. 2009 Jan;63(2):219–228.

Published In

Cancer Chemother Pharmacol

DOI

EISSN

1432-0843

Publication Date

January 2009

Volume

63

Issue

2

Start / End Page

219 / 228

Location

Germany

Related Subject Headings

  • Trastuzumab
  • Transfection
  • Signal Transduction
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Oxygen Consumption
  • Oncology & Carcinogenesis
  • Neovascularization, Pathologic
  • Neoplasm Transplantation
  • Mice, Nude