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Novel anticancer strategy moves from laboratory to clinic
Date:1/3/2008

search article, Dr. Durden and his colleagues show that a chemical inhibitor of all PI-3 kinases, modified with a tag that directs the compound to the blood vessels needed by growing tumors, stops the growth of seven types of tumors in mice.

The compound, called SF1126, is active against prostate, breast, renal, multiple myeloma, neuroblastoma, glioblastoma and rhabdomyosarcoma, the authors show.

The first author of the Cancer Research article is Joseph Garlich, PhD, chief scientific officer of Semafore Pharmaceuticals. The firm and Dr. Durden collaborated on identifying the SF1126 compound, based on his work while on the faculty at Indiana University School of Medicine.

At the end of 2007, doctors in Arizona and Indiana began to test SF1126 in a phase I clinical trial in people with solid tumors. Another phase I trial for multiple myeloma patients will begin at Emory's Winship Cancer Institute and elsewhere in 2008. It is anticipated that SF1126 will enter pediatric cancer trials within one year.

Scientists use PI-3 kinase inhibitors in test-tube experiments every day; however, the enzyme-inhibiting part of SF1126 was never used clinically despite its identification more than a decade ago.

"It was a total non-drug: toxic, insoluble and broke down too fast," Dr. Durden says.

Attaching the tag, called a RGD peptide, makes the inhibitor dissolve easier and last longer in the body. It also lets molecules on blood vessel walls grab the compound and send it into tumors, the authors show.

Tumors send out chemical signals for new blood vessels when they don't have enough oxygen. The authors found that in mice, the compound prevents tumors from growing new blood vessels by inhibiting part of their response to the lack of oxygen. SF1126 also sensitizes human tumors in mice to a chemotherapy agent called taxotere.

The authors found that tumor cell lines artificially engineered to be more "addicted" to P
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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University
Source:Eurekalert

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