Cancer Treat Rev 2015 Sep 19;41(8):680-9. Epub 2015 May 19.
Medical Oncology Service, HU Puerta de Hierro-Majadahonda, Onco-Hematology Area, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, Spain. Electronic address:
Anti-CD20 monoclonal antibodies (mAbs) have improved patient's survival with Non-Hodgkin Lymphoma, when combined with chemotherapy. Several mechanisms of action have been reported, including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and induction of apoptosis. Despite the large amount of studies and published data, the role each mechanism played in vivo is not fully understood. Furthermore, the reason why a significant percentage of patients are refractory or resistant remains unknown. Several activated intracellular signaling pathways have been implicated in the mechanisms of resistance of rituximab. In the present manuscript, we review those mechanisms and new anti-CD20 mAbs, as well as the efforts being accomplished to overcome it, focusing on new drugs targeting pathways implicated in resistance to rituximab.