Targeting the Central Dogma to Inhibit Nodes of Convergence in Cancer

Abstract

Cancer treatments often target singular oncoproteins in attempt to block one hallmark of cancer and stop tumor growth and progression. However, although these treatments are often initially effective, many cancer patients develop resistance and experience relapse due to redundant signaling or tumor heterogeneity. To avoid resistance mechanisms, cancer treatments must inhibit multiple hallmarks of cancer, and therefore multiple oncogenic signaling programs. One possible way to achieve this is to target nodes of convergence of oncogenic signaling, in which multiple oncogenic pathways depend on one protein for expression or signal proliferation. These nodes can be found within the central dogma processes that drive all cellular function. In this dissertation, this strategy is used to discover inhibitors of nodes involved in transcription, translation, and protein folding of oncogenes and oncoproteins. Targeting nodes of convergence may yield inhibitors that evade resistance mechanisms that plague current cancer therapies and provide superior clinical outcomes for cancer patients.