CA9 and neoplasm: Although APX2009 at 10 μM was sufficient to decrease CA9 expression in tumor alone 3D spheroids (without CAFs) (Fig. 2E), this concentration of APX2009 did not affect CA9 positivity in tumor +CAF co-culture spheroids (Figs 5E and S1F), suggesting that CAF cells are protective against the effects of APE1/Ref-1 redox inhibition in these cultures.