Dual targeting of PI3K and BCL-2 overcomes ibrutinib resistance in aggressive mantle cell lymphoma.

ABSTRACT: Despite significant efficacy of ibrutinib therapy in mantle cell lymphoma (MCL), about one-third of MCL patients will display primary resistance. In time, secondary resistance occurs almost universally with an unlikely response to salvage chemotherapy afterwards. While intense efforts are being directed towards the characterization of resistance mechanisms, our focus is on identifying the signalling network rewiring that characterizes this ibrutinib resistant phenotype. Importantly, intrinsic genetic, epigenetic and tumour microenvironment-initiated mechanisms have all been shown to influence the occurrence of the ibrutinib resistant phenotype. By using in vitro and in vivo models of primary and secondary ibrutinib resistance as well as post-ibrutinib treatment clinical samples, we show th

SUBMITTER: Ye H 

PROVIDER: S-EPMC9097828 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature