The small molecule inhibitor of the proteasome, bortezomib, promotes apoptosis; this effect appears to be due in part to prevention of NF-B activation, but the precise mechanisms have not been fully established38. Furthermore, the proteasome degrades proteins with a wide variety of cellular functions other than regulation of apoptosis (e.g. cell cycle proteins). While previous studies have shown clinical promise of bortezomib in lymphoma, including MCL39, the key signaling pathways modulated in responders and non-responders have not been characterized. Because bortezomib acts by inhibiting proteosomal degradation, its principal effects are expected to be observed at the protein level. Improving the survival of MCL is important and may be achieved with new targeted agents.
| Fu, Kai; Weisenburger, Dennis D; Greiner, Timothy C et al. (2005) Cyclin D1-negative mantle cell lymphoma: a clinicopathologic study based on gene expression profiling. Blood 106:4315-21 |
