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Paloma Pharmaceuticals to Present at the American Association for Cancer Research
Date:4/15/2008

ate cancer models that P529 enhances anti-tumor activity caused by radiation therapy. If P529 allows the radio-oncologist to use lower levels of radiation due to the radio-sensitizing effect of P529, this could translate into a reduction of side effects seen by radiation treatment including urinary tract dysfunction, impotence and an increase in rectal cancer," said Dr. Calvo.

"P529 is a potent inhibitor of angiogenesis and tumor growth," said Dr. Sherris. "Taken together, these presentations describe P529 as a broad acting anti-angiogenic and anti-tumor agent. Since tumor cells are known to release a large number of pro-angiogenic factors initiating tumor angiogenesis, to effectively inhibit angiogenesis one needs to inhibit not just one but if possible all of the factors. Single agent anti-cytokine therapy, such as anti-VEGF, has shown efficacy in the clinic but is limited by its ability to only target one pro-angiogenic factor. P529 has the ability to inhibit a range of disparate pro-angiogenic cytokines by inhibiting the pro-angiogenic factor's ability to transmit its signal through the cell as well as inhibiting the synthesis of pro-angiogenic factors through inhibition of HIF-1(alpha), a known regulator of the synthesis of pro-angiogenic cytokines by tumor cells. As P529 is shown to inhibit all tumor cell lines of the National Cancer Institute's 60 cell screen, and is shown here to inhibit multiple human tumor mouse xenograft models, P529 displays broad tumor cell activity. Furthermore, we show that P529 augments radiation therapy both in the test tube and in animal models. Such a response may result in lowering the dose of radiation used in radiotherapy thus reducing radiation side effects or perhaps potentiate radiotherapy efficacy. We believe all of these results are due to P529's ability to inhibit the PI3K/Akt/mTOR pathway through TORC1/TORC2 inhibition."

About Angiogenesis

Cancer, less than a few millimeters in size, utilizes nearby
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