However, monotherapy to inhibit IDO is ineffective in most patients with cancer and the IDO inhibitor epacadostat did not improve survival of patient with melanoma when combined with PD-1 blockade, raising questions about the role of IDO in resistance to therapy and the efficacy of IDO inhibitor drugs in patients with cancer.9 10 Nevertheless, regulatory pathways induced during tumor development (intrinsic) and/or responsive to therapy (adaptive) may mediate and potentiate resistance to therapy, respectively. The gene discussed is PDCD1; the disease is melanoma.