Shokat is an internationally renowned leader in studying protein kinases, the vital signaling molecules that are present in all cells. Kinases are responsible for most of the molecule-to-molecule communication in cells--cascades of signals that direct movement and metabolism, cancer and cell death.
By better understanding the role of the body's more than 500 different kinases, Shokat hopes to determine which of them should be targeted to treat diseases such as cancer and immune dysfunction. To achieve this goal, he and the members of his lab at UCSF combine the tools of synthetic organic chemistry, structural biology, genetics and mathematical modeling to gain insight into how signaling networks transmit information in both normal and disease settings.
In February, Shokat and his team announced a breakthrough: a new drug that successfully blocked cancer's main source of growth when tested in mice.
Far more potent than similar compounds already in clinical trial, the drug short-circuits the normal ability of cells to sense the need to grow and divide--a signal that cancer cells exploit to spread in the body.
Normally, a kinase in cells called mTOR integrates information about a cell's nutritional and energy needs and prompts the cell to manufacture key proteins for cell growth. Cancer then exploits this signal for its own growth.
The new drug, however, blocks each of the two mTOR signal pathways--a significant improvement over another drug currently being tested, rapamycin, which only blocks one pathway.
Dubbed a TORKinib because it inhibits the mTOR signal, the new compound is now being readied for clinical trials in patients. Shokat and his team plan to test the drug against a range of cancers--colorecta
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