In the present study, analysis of the combination of PKCβ inhibitor enzastaurin and the BTK inhibitor ibrutinib has shown synergistic anti-tumor effects in DLBCL, thereby providing a rational basis for future preclinical/clinical investigations that may allow for the development of specific, well tolerated and efficient cancer therapeutics for relapsed or refractory DLBCL patients. Here, BTK is linked to diffuse large B-cell lymphoma.