Inhibits PDK1-4, which normally phosphorylate and inactivate pyruvate dehydrogenase (PDH); DCA therefore reactivates PDH, diverting pyruvate from lactate toward acetyl-CoA and forcing increased TCA cycle flux. In SDH-INTACT glycolytic (Warburg) cancers this restores mitochondrial oxidative phosphorylation, elevates ROS, and reduces HIF-1α — the intended therapeutic effect demonstrated by Michelakis et al. (Sci Transl Med 2010, PMID 20463368). In SDH-DEFICIENT tumors the mechanism inverts and is potentially counterproductive: the TCA cycle is irreversibly blocked at the SDH step, so DCA-driven flux (citrate → isocitrate → α-KG → succinate) causes succinate to accumulate further at the blocked node, strengthening competitive inhibition of PHD1-3 and amplifying HIF-1α/HIF-2α pseudohypoxic signaling — the opposite of the desired effect. This amplification would also worsen succinate-driven CIMP epigenetic silencing (Killian et al., Cancer Cell 2013, PMID 23707781; Letouzé et al., Cancer Cell 2013, PMID 23550148). Additionally, SDH-deficient cells adaptively suppress Complex I activity to limit pyruvate oxidation pressure (Sokolov et al., bioRxiv 2025, PMID 42239110); DCA would override this adaptive compensation. No direct evidence of DCA efficacy in SDH-deficient tumor models exists; all published DCA-cancer data derive from SDH-intact glycolytic cancers. DCA is retained as a theoretical entry to flag this mechanistic safety concern — it should not be considered a candidate for SDH-deficient tumors without direct experimental evidence of benefit.