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Targeting Cancer through the Tumor Vasculature: Inhibiting cPLA(2) Sensitizes Tumors to Radiation Therapy

Strategic Insights

— 1 min read

Recent research published in the journal Clinical Cancer Research has identified a novel molecular target for tumor sensitization to radiation therapy through the tumor vasculature. The study, led by A. Linkous and colleagues at Vanderbilt University, found that inhibiting cPLA(2) with Arachidonyltrifluoromethyl Ketone (AACOCF(3)) significantly suppressed tumor growth and decreased overall tumor blood flow and vascularity. The researchers concluded that these findings identify cPLA(2) as a potential target for enhancing tumor response to radiation therapy.

Key Takeaways:

  • The study found that low doses of ionizing radiation trigger the activation of cPLA(2) in vascular endothelial cells, initiating prosurvival signaling that could be responsible for radioresistance of tumor vasculature.
  • Inhibiting cPLA(2) with AACOCF(3) prevented radiation-induced activation of ERK1/2 and decreased clonogenic survival of irradiated vascular endothelial cells.
  • Treatment with AACOCF(3) also attenuated tubule formation and migration in irradiated vascular endothelial cells.
  • In both tumor mouse models, treatment with AACOCF(3) prior to irradiation significantly suppressed tumor growth and decreased overall tumor blood flow and vascularity.
  • Increased apoptosis in both tumor cells and tumor vascular endothelium was determined as a possible mechanism of the observed effect.
  • The study suggests that cPLA(2) is a novel molecular target for tumor sensitization to radiation therapy through the tumor vasculature.
  • Vanderbilt University researchers have identified cPLA(2) as a potential target for enhancing tumor response to radiation therapy.

Statistics:

  • 1 µmol/L AACOCF(3) was used to treat vascular endothelial cells and lung tumor cells for 30 minutes prior to irradiation.
  • 10 mg/kg AACOCF(3) was administered daily for 5 consecutive days to mice with LLC or H460 tumors.
  • Tumor growth delay was assessed by measuring the time it took for the tumor to grow to a certain size.
  • Power Doppler Sonography and immunohistochemistry were used to evaluate treatment response in vivo.
  • Apoptosis was increased in both tumor cells and tumor vascular endothelium after treatment with AACOCF(3).

Sources:

  • A. Linkous, et al., "Cytosolic Phospholipase A2: Targeting Cancer through the Tumor Vasculature," Clinical Cancer Research, vol. 15, no. 5, 2009, pp. 1635-1644.
  • Vanderbilt University, Department of Radiation Oncology, School of Medicine, 1301 22nd Avenue S, B-902 Vanderbilt Clinic, Nashville, TN 37232, USA.
  • American Association for Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.

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