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First report that apoptotic and anti-angiogenic therapies work better together than alone
November 13, 2006Prague, Czech Republic: American researchers have found that giving a combination of imantanib (Glivec [1]) and a drug that induces cell death (apoptosis) was better at inhibiting the growth of Ewing's sarcoma in mice than either therapy on its own.
Imantanib works by preventing the creation of new blood vessels to supply the growing tumour (anti-angiogenesis) and the researchers believe that this is the first report of synergy between apoptosis and anti-angiogenic therapy in pre-clinical work.
Professor Andrea Hayes-Jordan reported to the EORTC-NCI-AACR [2] Symposium on Molecular Targets and Cancer Therapeutics in Prague today (Friday 10 November) that treating sarcoma cells with imantanib inhibited a growth factor called PDGFR-beta. This had the effect of increasing the sensitivity of the cells to a drug called tumour necrosis factor-related apoptosis-inducing ligand (TRAIL).
Prof Hayes-Jordan, assistant professor of surgery and pediatrics at the MD Anderson Cancer Center, Houston, USA, said: "When I treated the tumour cells with imantanib, the anti-angiogenic drug, the receptors for TRAIL, the apoptotic drug, increased, thus increasing the efficacy of TRAIL. This was supported by the mouse studies, which showed increased inhibition of pulmonary metastases and primary tumour growth when both were used simultaneously. These findings are important because, if it proves to be effective in humans, it would be well tolerated and have significantly fewer side effects than traditional cytotoxic therapy. Also, at present, we have no effective chemotherapy for pulmonary metastases - the only effective treatment is surgery - so this would give us another option."
Prof Hayes-Jordan hopes to investigate the dual therapy in humans in a clinical trial within 12-18 months.
Abstract no: 474
[1] Glivec is known as Gleevac or Gleevec in the USA.
[2] EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].
European Organisation for Research and Treatment of Cancer
Prof Hayes-Jordan, assistant professor of surgery and pediatrics at the MD Anderson Cancer Center, Houston, USA, said: "When I treated the tumour cells with imantanib, the anti-angiogenic drug, the receptors for TRAIL, the apoptotic drug, increased, thus increasing the efficacy of TRAIL. This was supported by the mouse studies, which showed increased inhibition of pulmonary metastases and primary tumour growth when both were used simultaneously. These findings are important because, if it proves to be effective in humans, it would be well tolerated and have significantly fewer side effects than traditional cytotoxic therapy. Also, at present, we have no effective chemotherapy for pulmonary metastases - the only effective treatment is surgery - so this would give us another option."
Prof Hayes-Jordan hopes to investigate the dual therapy in humans in a clinical trial within 12-18 months.
Abstract no: 474
[1] Glivec is known as Gleevac or Gleevec in the USA.
[2] EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].
European Organisation for Research and Treatment of Cancer
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