Drug slows prostate tumor growth by keeping vitami...(noid. These products known as retinoids ...),Health

Date:11/6/2007

noid. These products, known as retinoids, add all-trans retinoic acid (ATRA) to skin or cancer cells. VN/14-1, which is a retinoic acid metabolism blocking agent (RAMBA), works by inhibiting the breakdown of ATRA, keeping more retinoic acid available within cancer cells so that the chemical can redirect these cells back into their normal growth patterns, which includes programmed cell death.

Our idea is that rather than give extra ATRA, we would prevent ATRA already available within cells from being broken down, Njar said. We now call VN/14-1 an atypical RAMBA because in addition to blocking ATRA metabolism, it has other multiple desirable anti-cancer effects.

VN/14-1 works by blocking the CYP26 enzyme that actually transforms ATRA into inactive compounds, he says. The researchers have successfully tested VN/14-1 in breast cancer cells and have been funded to study the compound in preclinical studies that can lead to a Phase I human clinical trial.

In this study, the researchers found in mouse models of human prostate cancer that a 5 mg/kg (milligram per kilogram) dose injected daily resulted in a 33 percent reduction in tumor size; a dose twice as large reduced tumors by 50 percent.

They also tested a dose of 20 mg/kg through oral and intravenous administration to study the concentration of VN/14-1 in the blood over time in rats. They found that the amount of VN/14-1 in the blood after oral administration was exceptionally high compared to intravenous VN/14-1. This indicates that VN/14-1 should be tested orally as this is the preferred route of drug administration in humans, Njar says. Giving an agent orally in small doses is exactly what you want in an anti-cancer drug, he said.

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Contact: Staci Vernick Goldberg staci.goldberg@aacr.org 267-646-0616 American Association for Cancer Research Source:Eurekalert

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