Oncogene
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Rituximab, a chimeric monoclonal antibody targeted against the pan-B-cell marker CD20, was the first monoclonal antibody to be approved for therapeutic use. Treatment with rituximab at standard weekly dosing is effective in more than 50% of patients with relapsed or refractory CD20-positive follicular non-Hodgkin's lymphoma, but is not curative. It is less effective in other subtypes of CD20-positive lymphoma and for retreatment, even with CD20 still expressed. ⋯ Thus, the role of various resistance pathways, some documented in experimental systems and others still hypothetical, remains uncertain. Resistance could potentially be mediated by alterations in CD20 expression or signaling, elevated apoptotic threshold, modulation of complement activity or diminished cellular cytotoxicity. As the first of an expanding class of anticancer agents, lessons learned regarding the mechanism of rituximab action and resistance will be of increasing importance.