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UCLA scientists uncover mechanism of response to targeted therapy

ff the independent blood supply that cancers need to grow and flourish. The CCI-779 would stop the growth of the cancer, and the chemotherapy would be used to kill the cancer cells or the angiogenesis inhibitor could be administered to cut off the blood supply to the tumor, stopping the flow of oxygen and nutrients that the tumor needs to survive.

Standard of care for kidney cancer is almost always removal of part or the entire kidney, so that tissue could be tested for the molecular signature that indicates response to CCI-779. Doctors could then decide on what treatment to use in those likely to respond to the drug.

A secondary study finding determined that the drug's efficacy can be monitored quickly using positron emission tomography (PET). Because HIF also regulates glucose transport in cells, UCLA researchers theorized that the kidney cancer cells, with their high levels of HIF, would take in a standard PET imaging probe at high levels. If that proved true, the PET scan would show that the cancer cells had increased levels of the probe. Using laboratory animals, researchers determined that kidney cancer cells were indeed better at taking up the probe, allowing the cancer cells to be monitored by PET scanning. Just 24 hours after treatment with CCI-779, intake of the PET probe levels dropped in the cancer cells, meaning HIF levels were falling and the drug was working.

"If we can use PET scanning to follow response, patients won't need repeated invasive tests," Thomas said. "This would save them from getting an added surgical procedure. And we can see, in a very short time, probably in less than a week, whether the drug is working."

The study was a collaboration of researchers from the Jonsson Cancer Center, the Crump Institute for Molecular Imaging, the Howard Hughes Medical Institute and the UCLA departments of pathology, urology, medicine and molecular and medical pharmacology.


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Source:University of California - Los Angeles


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