Understanding the Mechanisms of Resistance to Rituximab: Paving the Road for the Development of Therapeutic Strategies to Overcome Rituximab-Resistance

摘要: Rituximab-resistance is an emerging challenge for both the scientific community and practicing oncologist. Parallel to improvement clinic outcomes, incorporation of rituximab into management patients with B-cell lymphoma appears be changing biology relapsed/refractory disease. At least in diffuse large (DLBCL), previously established salvage rituximab-chemotherapy-based treatments [including high dose chemotherapy autologous stem cell support (HDC-ASCS)] are less effective failing immunochemotherapy induction. The estimated 3-year failure free survival treated R-CHOP DLBCL following HDC-ASCT only 33 %, stressing need to: (1) understand mechanisms responsible rituximab-resistance, (2) identify cellular pathways playing a pivotal role acquired resistance (3) develop novel therapeutic strategies overcome or circumvent rituximab-resistance lymphoma. Pre-clinical models study have been generated characterized. Moreover, repeated exposure cells rituximab, not results decrease anti-tumor activity, but also cross-resistance multiple agents (suggesting shared resistance). Insightful information regarding biological basis paving next generation clinical trials evaluating monoclonal antibodies, immunoconjugates, and/or targeted aimed at blocking key-regulatory proteins associated resistance. Here, we provide general overview that identified so far review some early interventions being tested pre-clinical rituximab-resistant