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Isolating Malignant and Non-Malignant B Cells from lck:eGFP Zebrafish
Published on: February 22, 2019
Resistance to Ibrutinib in B Cell Malignancies: One Size Does Not Fit All
Bijal Shah1, Xiaohong Zhao1, Ariosto S Silva2
1Department of Malignant Hematology and Department of Chemical Biology and Molecular Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Abstract:
Ibrutinib resistance, as a result of coordinated rewiring of signaling networks and enforced tumor microenvironment (TME)-lymphoma interactions, drives unrestrained proliferation and disease progression. To combat resistance mechanisms, we must identify the compensatory resistance pathways and the central modulators of reprogramming events. Targeting the transcriptome and kinome reprogramming of lymphoma cells represents a rational approach to mitigate ibrutinib resistance in B cell malignancies. However, with the apparent heterogeneity and plasticity of tumors shown in therapy response, a one size fits all approach may be unattainable. To this end, a reliable and real-time drug screening platform to tailor effective individualized therapies in patients with B cell malignancies is warranted. Here, we describe the complexity of ibrutinib resistance in B cell lymphomas and the current approaches, including a drug screening assay, which has the potential to further explore the mechanisms of ibrutinib resistance and to design effective individualized combination therapies to overcome resistance and disable aggressive lymphomas (see Outstanding Questions).
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