To further test the notion that activation of ISR and GCN2 were critical for the desired response of tumor cell death following Ref-1 inhibition, we utilized a GCN2 inhibitor (GCN2iB) or a GCN2 activator, halofuginone (HF) in combination experiments with Ref-1 inhibition. The gene discussed is EIF2AK4; the disease is neoplasm.