Ribosome-directed cancer therapies: the tip of the iceberg?

Ribosomes and ribosome biogenesis (RiBi) are universally corrupted in cancer, fueling the high rates of translation that sustain malignancy and creating opportunities for discriminating therapeutic intervention. Despite longstanding recognition of the promise of ribosome-directed cancer therapies, only a handful of such agents have been used in the clinic, and with limited success, and the true potential of this approach is unknown. In the past few years, however, understanding of cancer ribosome specialization and the intricacies of RiBi have advanced dramatically, opening opportunities that could not be imagined when existing agents were discovered. Here, we discuss the rationale for targeting ribosomes to treat cancer, review the limitations of current agents, and highlight an important set of recent discoveries we propose could be exploited to discover molecularly-targeted ribosome-directed cancer therapeutics.