Thesis / Dissertation

Defining the translational landscape of MYC-driven cancer cells in response to therapeutic targeting of the ribosome

Eric Kusnadi, Richard Pearson (ed.)

Published : 2018

Abstract

Recent studies by our group and others have demonstrated that oncogene- driven hyper-activation of ribosome synthesis and activity is a vulnerability that can be targeted for cancer treatment. Specifically, combined inhibition of ribosome synthesis using the Pol I inhibitor CX-5461 and mTORC1-dependent mRNA translation using everolimus (EV) synergistically improved survival benefit of a MYC-driven mouse model of B-lymphoma [1]. Despite this promising outcome, a few questions remain: 1) what are the molecular mechanisms that trigger the pro-death pathways in these lymphoma cells in response to CX-5461-everolimus co-treatment (CX-5461+EV); 2) what mechanisms confer resistance to this combinati..

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