However, many clinical trials targeting DR4/5 using monoclonal antibodies have not reached the desirable anti-tumor efficacy, which could be due to inhibition of apoptosis at different signaling transduction stages, such as blocking the death-inducing signaling complex (DISC) level by c-FLIP, or more downstream, at the mitochondrial level by overexpression of IAP or Bcl-2 family members, leading to cell death resistance as shown by our and other laboratories34,39. The gene discussed is BCL2; the disease is neoplasm.