This $560,458 project grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) supports research at Children's Mercy Hospital to develop novel anti-cancer therapies that selectively target cancer cells deficient in the p53 tumor suppressor gene. The key objectives are to:
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Determine how simultaneous induction of reactive oxygen species (ROS)-mediated DNA damage and inhibition of the DNA damage response (DDR) can efficiently trigger p53 synthetic lethality in cancer cells.
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Evaluate the in vivo efficacy, safety, and pharmacological properties of the lead KU-D2 and KU-D2F compounds in preclinical osteosarcoma models, including patient-derived xenografts.
This 5-year project, running from March 2025 to February 2030, aims to identify innovative therapeutic strategies that exploit cancer-specific vulnerabilities imposed by p53 deficiency, a common driver of many tumor types. The research outcomes could lead to the development of new anti-cancer drugs with enhanced selectivity and reduced side effects.
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