Combination Therapy Targeting Ribosome Biogenesis and mRNA Translation Synergistically Extends Survival in MYC-Driven Lymphoma
Devlin, J. R; Hannan, Katherine; Hein, N; Cullinane, C; Kusnadi, E; Ng, P. Y; George, A. J; Shortt, J; Bywater, M. J; Poortinga, G; Sanij, E; Kang, J; Drygin, D; O'Brien, S; Johnstone, R. W; McArthur, G. A; Hannan, R. D; Pearson, R. B
UNLABELLED Ribosome biogenesis and protein synthesis are dysregulated in many cancers, with those driven by the proto-oncogene c-MYC characterized by elevated Pol I-mediated ribosomal rDNA transcription and mTORC1/eIF4E-driven mRNA translation. Here, we demonstrate that coordinated targeting of rDNA transcription and PI3K-AKT-mTORC1-dependent ribosome biogenesis and protein synthesis provides a remarkable improvement in survival in MYC-driven B lymphoma. Combining an inhibitor of rDNA...[Show more]
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