Anti-ERBb4 targeted therapy combined with radiation therapy in prostate cancer. Results of in vitro and in vivo studies

Cancer Biol Ther. 2008 Jul;7(7):1090-4. doi: 10.4161/cbt.7.7.6167. Epub 2008 Apr 19.

Abstract

Purpose: To evaluate the efficiency of anti ErbB4 targeted therapy combined with irradiation (XRT) over each modality alone in prostate cancer.

Results: Clones with high ErbB4 expression grew faster than those with low ErbB4 expression. XRT inhibited the growth of both expressive and non-expressive ErbB4 cells, while mAb inhibited only high ErbB4-expressing cells. The combination of XRT and mAb resulted in a 30% reduction of the survival of high ErbB4 expressing cells over XRT alone (p = 0.013). In tumor bearing mice the tumor size in the combined arm was 1 mm at 4 weeks compared to 2-3 mm and 4-5 mm in the radiation and mAb arms (p' value of 0.02 and 0.087 respectively).

Methods: Clones with low and high expression of ErbB4 isolated by a limited dilution technique from an androgen-independent Cl-1 cell line were used. The cells from these clones were exposed to XRT (single dose of 2-6 Gy) and to anti-ErbB4 monoclonal antibody (mAb). The XTT test was used to measure cell survival. In addition, tumor-bearing nude mice were treated either by XRT, mAb or by a combined treatment. Tumor sizes were recorded at given time points.

Conclusion: Anti ErbB4 combined with XRT is possibly more effective than each modality alone in prostate cancer.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Combined Modality Therapy
  • Drug Screening Assays, Antitumor
  • ErbB Receptors / chemistry*
  • ErbB Receptors / immunology
  • Humans
  • Immunotherapy / methods
  • Male
  • Mice
  • Mice, Nude
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / therapy*
  • Receptor, ErbB-4
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • ERBB4 protein, human
  • ErbB Receptors
  • Erbb4 protein, mouse
  • Receptor, ErbB-4