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Combination targets: some drugs may work best when they work together
Date:10/24/2007

xia-related protein involved in stabilizing cells in the absence of oxygen, said Aoife M. Shannon, Ph.D., a postdoctoral fellow at the University of Manchester. Furthermore, HIF is associated with protecting tumors from the effects of radiation

As a cancer treatment, radiotherapy, which works by damaging DNA with ionizing radiation, is relatively less effective against tumors that are deprived of oxygen, or hypoxic, the researchers say. As tumors grow into large masses, they strain the available supply of oxygen and exist in a hypoxic state.

Shannon and her colleagues studied the combined effects of radiation and AZD6244 on human lung cancer cell cultures and a mouse model of human lung cancer, in studies funded by AstraZeneca. In mice they found that the combination of radiotherapy and drug was more effective than either therapy alone. While the drug alone and the combination therapy caused the tumors to shrink to nearly a third of their original volume within 10 days, regrowth took significantly longer in the combination group than in the drug- or radiation-only groups.

According to Shannon, their findings support further development of AZD6244 and radiotherapy as combined regimen, and indicate a novel role for AZD6244 in inhibiting the tumor hypoxia response.

It is possible that the effect of AZD6244 on HIF as well as tumor blood vessel growth induced by HIF contributed towards the remarkable effects of the combination, Shannon said. It is a double-pronged approach that will likely be relevant to ongoing trials of MEK inhibitors and inform future studies.

Identifying strategies to enhance responses induced by EGFR kinase inhibitors in mutant EGFR-dependent lung adenocarcinomas: Abstract A 248.

Researchers at Memorial Sloan-Kettering Cancer Center have developed a strategy to enhance tumor response in some lung cancer patients treated with the tyrosine kinase inhibitor (TKI), erlotinib, by combi
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Contact: Greg Lester
greg.lester@aacr.org
267-646-0554
American Association for Cancer Research
Source:Eurekalert

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