ABSTRACT
Introduction
The ribosome is a ribonucleoprotein organelle responsible for protein synthesis, and its biogenesis is a highly coordinated process that involves many macromolecular components. Any acquired or inherited impairment in ribosome biogenesis or ribosomopathies is associated with the development of different cancers and rare genetic diseases. Interference with multiple steps of protein synthesis has been shown to promote tumor cell death.
Areas covered
We discuss the current insights about impaired ribosome biogenesis and their secondary consequences on protein synthesis, transcriptional and translational responses, proteotoxic stress, and other metabolic pathways associated with cancer and rare diseases. The modulation of different therapeutic chemical entities targeting cancer in in vitro and in vivo models have also been detailed.
Expert opinion
Despite the association between inherited mutations affecting ribosome biogenesis and cancer biology, the development of therapeutics targeting the essential cellular machinery has only started to emerge. New chemical entities should be designed to modulate different checkpoints (translating oncoproteins, dysregulation of specific ribosome-assembly machinery, ribosomal stress, and rewiring ribosomal functions). Although safe and effective therapies are lacking, consideration should be given to using existing drugs alone or in combination for long-term safety, with known risks for feasibility in clinical trials and synergistic effects.
Article highlights
Ribosomes are complex machinery, and their biogenesis is responsible for protein synthesis in all living cells.
Association between impairment of ribosome biogenesis and an increased risk of cancer has been established.
Understanding the secondary consequences and different cellular checkpoints of impaired ribosome biogenesis could provide a platform for the design and development of novel anticancer therapies.
The availability of a wide spectrum of potential inhibitors and their potential for translation into viable clinical opportunities to treat cancer are discussed.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in this manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, or patents received or pending, and royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.