Combining virotherapy and angiotherapy for the treatment of breast cancer

M Bazan-Peregrino1, R C A Sainson, R C Carlisle

  • 1Department of Oncology, Old Road Campus, University of Oxford, Oxford, UK.

Cancer Gene Therapy
|July 13, 2013
PubMed

Insights

Engineered oncolytic adenovirus targets breast cancer by inhibiting vascular endothelial growth factor (VEGF) and Notch signaling. This dual approach enhanced efficacy in ER-negative tumors, doubling survival time and reducing tumor vascularization.

Area of Science:

  • Oncolytic virotherapy
  • Cancer biology
  • Tumor angiogenesis

Background:

  • Oncolytic adenoviruses offer selective cancer cell lysis.
  • Tumor growth is supported by angiogenesis (new blood vessel formation).
  • VEGF and Notch signaling pathways are crucial for angiogenesis.

Purpose of the Study:

  • To engineer an oncolytic adenovirus expressing VEGF and Notch antagonists.
  • To evaluate the combined anti-cancer and anti-angiogenic effects.
  • To assess efficacy in estrogen receptor-positive and negative breast cancer models.

Main Methods:

  • Engineered AdEHE2F adenovirus to express soluble Flt-1 (sFlt1) and soluble Dll4 (sDll4).
  • Assessed in vitro effects on endothelial cells.
  • Evaluated in vivo efficacy in ER-positive (ZR75.1) and ER-negative (MDA-231) breast cancer xenografts.

Main Results:

  • In vitro, sFlt1 inhibited endothelial proliferation, while sDll4 increased vascular branching.
  • In ER-positive tumors, AdEHE2F showed virotherapy alone; sFlt1/sDll4 did not augment efficacy.
  • In ER-negative tumors, AdEHE2F encoding sFlt1 or sDll4 doubled survival and reduced tumor vascularization.

Conclusions:

  • Combined anti-VEGF and anti-Notch strategies enhance oncolytic adenovirus efficacy in ER-negative breast cancer.
  • The enhanced efficacy is attributed to synergistic anti-tumor and anti-vascular effects.
  • This dual-targeting approach holds promise for treating specific breast cancer subtypes.

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