Mantle cell lymphoma: biological insights and treatment advances.
Mantle cell lymphoma (MCL) exhibits considerable molecular heterogeneity and complexity, and is regarded as one of the most challenging lymphomas to treat. With increased understanding of the pathobiology of MCL, it is proposed that MCL is the result of 3 major converging factors, namely, deregulated cell cycle pathways, defects in DNA damage responses, and dysregulation of cell survival pathways. In the present era of targeted therapies, these biologic insights have resulted in the identification of several novel rational targets for therapeutic intervention in MCL that are undergoing active clinical testing. To date, there is no standard of care in MCL. Several approaches including conventional anthracycline-based therapies and intensive high-dose strategies with and without stem cell transplantation have failed to produce durable remissions for most patients. Moreover, considering the heterogeneity of MCL, it is increasingly being recognized that risk-adapted therapy might be a relevant therapeutic approach in this disease. At the first and second Global Workshops on Mantle Cell Lymphoma, questions addressing advances in the pathobiology of MCL, optimization of existing therapies, assessment of current data with novel therapeutic strategies, and the identification of molecular or phenotypic risk factors for utilization in risk-adapted therapies were discussed and will be summarized herein.
Leonard
John P
JP
Center for Lymphoma and Myeloma, Clinical Research, Division of Hematology/Oncology, New York Weill Cornell Medical Center, New York, NY, USA. jpleonar@mail.med.cornell.edu
Williams
Michael E
ME
Goy
Andre
A
Grant
Steven
S
Pfreundschuh
Michael
M
Rosen
Steve T
ST
Sweetenham
John W
JW
D002453:Cell Cycle; D002470:Cell Survival; D004249:DNA Damage; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D012074:Remission Induction