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metformin + cytarabine
- Development stage
- Unknown
- Lead developer
- Northwestern University
- Modality
- Small Molecules
- Administration
- Oral, Intravenous
01
Overview
Metformin + cytarabine is an investigational combination therapy being evaluated for the treatment of relapsed or refractory acute myeloid leukemia (AML). This regimen, specifically studied in a Phase I trial led by Northwestern University, repurposes the biguanide metformin—traditionally used for type 2 diabetes—as an adjunct to the standard chemotherapy agent cytarabine (Ara-C). Metformin's anti-leukemic activity is attributed to its ability to inhibit mitochondrial oxidative phosphorylation (OXPHOS) and modulate key metabolic and survival pathways, including the activation of AMP-activated protein kinase (AMPK) and the inhibition of the mTOR and AKT/HIF1A/PDK1 signaling axes. By targeting the metabolic vulnerabilities of leukemia stem cells and resistant blasts, metformin is hypothesized to sensitize AML cells to the cytotoxic effects of cytarabine, which acts by inhibiting DNA polymerase and disrupting DNA synthesis.
- Other names
- metformin hydrochloridecytarabineAra-C
02
Targets
DNA polymerase familyAMPK (Adenosine monophosphate–activated protein kinase)ND1 (Mitochondrial electron transport chain complex I)
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