Mantle cell lymphoma: identifying novel molecular targets in growth and survival pathways.

Mantle cell lymphoma (MCL) remains one of the more challenging sub-types of non-Hodgkin lymphoma. This entity, which is only approximately 10 years old, is characterized by response to many different chemotherapy regimens, though the duration of those responses remains often times quite short. Retreatment with second and third line combination regimens results in shorter and shorter durations of response, with the rapid emergence of a very drug-resistant phenotype. Despite these often frustrating clinical features, there is now a lot of new hope in managing patients with MCL. New insights into the molecular pathogenesis of MCL has revealed a plethora of new potential targets, while our continued efforts in novel targeted drug development has produced a host of agents that are already helping patients with this challenging disease. The use of proteasome inhibitors, for example, represents one example of a new strategy that has offered new hope for patients, and new opportunities for the physician treating this disease. In this review, we will put this biology into perspective, and describe how new revelations in MCL pathogenesis are leading to the identification of many exciting new drugs with promising activity.