Interrogating B cell signaling pathways: A quest for novel therapies for mantle cell lymphoma

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Science Signaling  05 Feb 2019:
Vol. 12, Issue 567, eaat4105
DOI: 10.1126/scisignal.aat4105


Mantle cell lymphoma (MCL) is a rare and aggressive B cell lymphoma, which is often resistant to chemotherapy. Understanding how B cell signaling and activity are deregulated in MCL, and harnessing therapeutic targets therein, will improve survival rates among patients. In this review, which includes 3 figures, 2 tables, and 73 references, we discuss the regulatory pathways in B cells that contribute to the pathogenesis of MCL and highlight potential targets along those routes, the inhibitors that are currently in preclinical or clinical trials, and how to make such targeted therapeutics more effective for patients.


Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma that is largely chemoresistant. Ibrutinib, a drug that inhibits Bruton’s tyrosine kinase (BTK), has improved the overall survival of patients with MCL; however, resistance to ibrutinib has emerged as a decisive, negative factor in the prognosis of MCL. Adopting a more patient-centric therapeutic approach that incorporates applied genomics and interrogation of B cell signaling pathways may offer an alternative route to reach durable remission in patients with MCL. Although targeting genetic variants in MCL is not yet feasible in the clinical setting, the identification and targeting of increasingly active B cell signaling pathways may be a viable therapeutic strategy that may improve patient outcomes. Genome-editing tools and sequencing platforms could play dominant roles in patient-centric approaches of treatment in the future, potentially improving clinical outcomes for patients with MCL.

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