Targeting Angiotensin II Type 1 Receptors for Ovarian Cancer Therapy

Strategic Insights -

Scientists in Japan have identified the angiotensin II type 1 receptor as a potential target for ovarian cancer therapy. According to a study published in Clinical Cancer Research, this receptor is expressed in a significant proportion of invasive ovarian adenocarcinomas and is involved in tumor progression and angiogenesis. The researchers found that blocking this receptor with a specific blocker, candesartan, not only inhibited the invasive potential and vascular endothelial growth factor (VEGF) secretion in ovarian cancer cells but also reduced peritoneal dissemination and suppressed tumor angiogenesis in a mouse model.

Key Takeaways:

  • The angiotensin II type 1 receptor (AT[subscript]1R) was expressed in 85% of invasive ovarian adenocarcinomas, 66% of borderline malignant tumors, and 14% of benign cystadenomas.
  • AT[subscript]1R expression was associated with increased VEGF expression intensity and intratumor microvessel density in invasive carcinomas.
  • The AT[subscript]1R blocker candesartan completely inhibited the invasive potential and VEGF secretion in AT[subscript]1R-positive SKOV-3 ovarian cancer cells.
  • Administration of candesartan into SKOV-3-transplanted athymic mice resulted in the reduction of peritoneal dissemination, decreased ascitic VEGF concentration, and suppression of tumor angiogenesis.
  • AT[subscript]1R blockade therapy may become a novel and promising strategy for ovarian cancer treatment.

Statistics:

  • 57 of 67 (85%) invasive ovarian adenocarcinomas expressed AT[subscript]1R.
  • 12 of 18 (66%) borderline malignant tumors expressed AT[subscript]1R.
  • 2 of 14 (14%) benign cystadenomas expressed AT[subscript]1R.
  • VEGF expression intensity and intratumor microvessel density were significantly higher in cases strongly positive for AT[subscript]1R compared to weakly positive or negative cases.

Sources:

  • Suganuma et al., Functional expression of the angiotensin II type 1 receptor in human ovarian carcinoma cells and its blockade therapy resulting in suppression of tumor invasion, angiogenesis, and peritoneal dissemination. Clin Cancer Res, 2005;11(7):2686-2694.
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