The constitutive activation of the transcription factor nuclear-factor kappa B (NF-kappaB) is a hallmark of many highly malignant tumours such as the pancreatic ductal adenocarcinoma and accounts for profound chemoresistance. Inhibition of NF-kappaB activation has been shown to be a useful strategy for increasing the sensitivity towards cytostatic drug treatment in vitro and in vivo. Moreover, various pharmacological substances (e.g. thalidomide, bortezomib, sulphasalazine) have already entered clinical studies partially showing promising results for certain types of cancer. Further studies will be needed, in particular for pancreatic ductal adenocarcinoma, to evaluate the therapeutic efficacy of appropriate combinations of a NF-kappaB inhibitor and cytostatic drugs.