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The risk of rebound disease activity is unknown, so it’s unclear whether clinicians would be compelled to use it during pregnancy as with natalizumab

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Notably, breast cancer cells achieve metabolic adaptation by hijacking the autophagy mechanism: under glucose-deprivation conditions, MANF-mediated mitophagy eliminates dysfunctional mitochondria through the PRKN/Parkin-dependent pathway, maintains the ATP supply and promotes tumour survival [112], suggesting that targeting the MANF‒PRKN interaction can break the drug resistance barrier of breast cancer under metabolic stress