Blockade of the anti-apoptotic proteins Bcl-2 and Bcl-XL through Ref-1/APE1’s redox inhibition of STAT3 activity contributes to the enhanced cell killing and tumor growth seen in this combination.244 Furthermore, in NSCLC cell line A549, siRNA inhibition of Ref-1/APE1 expression significantly sensitizes A549 cells to cisplatin and increased cell apoptosis.202 Both of these studies point to Ref-1/APE1 function as critical in the cells’ response to cisplatin, especially in apoptosis signaling through STAT3. The gene discussed is STAT3; the disease is non-small cell lung carcinoma.