3D map of cell signaling sites could help improve cancer treatment
Cell-communication molecules called kinases play a key role in the growth and spread of many cancers. But exactly which kinases are active in a particular cancer is not always clear—there are 1.8 million sites on human proteins that kinases might act on, and researchers have fully characterized fewer than 1% of them.
3D mapping of kinase binding sites using AI tool KinoPlex could improve cancer treatment options. Kinases are proteins that add phosphate groups to other proteins, influencing cell growth, division, metabolism and other essential functions. Mutations in kinases can contribute to cancer development. There are 1.8 million potential kinase binding sites on human proteins, but researchers have only characterized fewer than 1% of them.
To address this gap, a team from Harvard Medical School developed KinoPlex, an AI-enabled tool that maps the three-dimensional structures of all kinase binding sites and identifies which kinases can interact with them. In a study published in Nature Biotechnology, the researchers demonstrated that KinoPlex can determine which kinases are active in specific cancer cells.
By analyzing a patient's particular cancer, mutations, and phosphorylation state, KinoPlex could help doctors predict which of around 100 existing kinase-inhibiting treatments would be most effective for a particular patient. The tool may also reveal targets for future cancer therapeutics. Researchers partnered with oncologists at several hospitals to test KinoPlex with clinical samples from cancer patients.
They found that KinoPlex successfully identified kinase signals associated with leukemia growth and survival in leukemia cells. With over 90 FDA-approved kinase-inhibiting drugs available, KinoPlex aims to support and improve these treatments by providing a more accurate prediction of which drugs would be most effective for each patient's specific cancer.
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