This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $734,435 to the Beckman Research Institute of the City of Hope to conduct research aimed at overcoming resistance to BH3 mimetic drugs, a class of targeted cancer therapies, in acute myeloid leukemia (AML). The key objectives of the research are to: 1) Determine how upregulation of the ADSS2 enzyme, which is involved in AMP biosynthesis, contributes to BH3 mimetic drug resistance in AML; 2) Define the mechanistic relationship between ADSS2 activity, AMPK signaling, and mitochondrial vulnerability in drug-resistant AML; and 3) Evaluate the efficacy of combining BH3 mimetic drugs with a novel ADSS inhibitor compound to eliminate AML in preclinical models. The award period runs from March 2025 through February 2030. The research seeks to provide insights that could support the development of improved combination therapies for AML patients resistant to current BH3 mimetic-based regimens.
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