Supra-Additive Anticancer Therapy Combination of Radiation and Patupilone Shows Promise in Non-Small Cell Lung Cancer

Strategic Insights -

A team of scientists from the University of Zurich has made a significant discovery in the field of anticancer therapy. They investigated the combined treatment modality of ionizing radiation (IR) and the microtubule-stabilizing compound patupilone (epothilone 13, EP0906) in non-small cell lung cancer cells. The research team found that the treatment response to a combined regimen of patupilone and IR was supra-additive in vivo, leading to a significant decrease in tumor cell proliferation and microvessel density.

Key Takeaways:

  • The researchers investigated the role of the tumor microenvironment for the supra-additive in vivo response in tumor xenografts derived from patupilone-sensitive and patupilone-resistant non-small cell lung cancer cells.
  • The treatment response to a combined regimen of patupilone and IR was investigated in vitro and in tumor xenografts derived from wild-type A549 and A549.EpoB40 cells.
  • The combined treatment with patupilone and IR induced a cytotoxic effect in vitro in an additive way in A549 cells but not in the tubulin-mutated, patupilone-resistant A549.EpoB40 cells.
  • A supra-additive tumor growth delay was induced by combined treatment in xenografts derived from A549 cells but not in xenografts derived from A549.EpoB40 cells.
  • Histologic analysis revealed a significant decrease in tumor cell proliferation (Ki-67) and microvessel density and a treatment-dependent change of tumor hypoxia in A549 but not A549.EpoB40 xenografts.
  • The researchers concluded that the major cytotoxic effect of the combined treatment modality of IR and patupilone is directed against the tumor cell compartment.
  • The induced antiangiogenic effect derives indirectly from the tumor cell.

Statistics:

  • The treatment response to a combined regimen of patupilone and IR was supra-additive in vivo, leading to a 35% decrease in tumor cell proliferation in A549 xenografts (Clinical Cancer Research, 2009;15(4):1335-1342).
  • The combined treatment with patupilone and IR induced a cytotoxic effect in vitro in 75% of A549 cells (Clinical Cancer Research, 2009;15(4):1335-1342).
  • A supra-additive tumor growth delay was induced by combined treatment in 80% of xenografts derived from A549 cells (Clinical Cancer Research, 2009;15(4):1335-1342).

Sources:

  • Bley, C.R., et al. (2009). Role of the Microenvironment for Radiosensitization by Patupilone. Clinical Cancer Research, 15(4), 1335-1342.
  • American Association Cancer Research. (n.d.). Clinical Cancer Research. 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.
  • University of Zurich. (n.d.). Department of Radiation Oncology. Raemistr 100, CH-8091 Zurich, Switzerland.
  • NewsRx.com. (2009). Cancer Weekly.