Open Access
Article
Understanding rituximab function and resistance: implications for tailored therapy
Alfredo Amoroso1,Sameh Hafsi1,Loredana Militello1,Alessia E Russo1,Zohra Soua1,Maria C Mazzarino1,Franca Stivala1,Massimo Libra1
1
Department of Biomedical Sciences, University of Catania, Catania, Italy
DOI: 10.2741/3719 Volume 16 Issue 2, pp.770-782
Published: 01 January 2011
(This article belongs to the Special Issue Novel strategies for detection, prevention and treatment of cancer)
Abstract

The addition of anti-CD20 monoclonal antibody (rituximab) to chemotherapy has significantly improved survival in B-cell lymphoma. However, a substantial number of patients relapse after treatment with rituximab. Understanding of anti-CD20 antibody molecular function may facilitate the development of pharmacologic strategies to overcome resistance. Cell death have been demonstrated to be caused by rituximab binding to CD20 throughout direct and indirect mechanisms. The direct mechanism comprises growth inhibition, induction of apoptosis and sensitization of cells to chemotherapy. While, the indirect mechanisms to Rituximab include complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). However, these mechanisms are still poorly understood. To shed light on this issue, we have analyzed the most significant results showing the role of Rituximab as a signal-inducing antibody and as a chemosensitizing agent through negative regulation of major survival pathways. Mechanisms of resistance to Rituximab are also discussed. Additionally, studies here reported show that, cellular targets are modified after treatment with Rituximab and may become useful for novel therapeutic strategies in the treatment of patients resistant to standard therapy.

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Alfredo Amoroso, Sameh Hafsi, Loredana Militello, Alessia E Russo, Zohra Soua, Maria C Mazzarino, Franca Stivala, Massimo Libra. Understanding rituximab function and resistance: implications for tailored therapy. Frontiers in Bioscience-Landmark. 2011. 16(2); 770-782.