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. 2019 Aug 14;11:7673–7684. doi: 10.2147/CMAR.S210004

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© 2019 Czogalla et al.

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Summary of the hypothesized interaction within the NRF2/AKR1C1/PR pathway.

Notes: Activated NRF2 (high nuclear, low cytoplasmic expression) activates aldo-keto reductase family 1 member C1 (AKR1C1) via an antioxidant response element (ARE). AKR1C1 converts progesterone to its inactive form, the 20-alpha-dihydroxyprogesterone, and decreases PR receptor activity with consecutive platinum resistance. Metformin treatment counteracts this pathway, which may reverse the effects and consecutively lead to platinum re-sensitization.