Ribosomopathies and cancer: pharmacological implications

Area of Science:

• Molecular Biology
• Oncology
• Genetics

Background:

• Ribosomes are essential for protein synthesis; ribosome biogenesis is a complex, coordinated process.
• Impaired ribosome biogenesis (ribosomopathies) is linked to various cancers and rare genetic disorders.
• Disrupting protein synthesis can induce cancer cell death.

Purpose of the Study:

• To review current understanding of impaired ribosome biogenesis and its impact on cellular processes.
• To discuss the consequences of these impairments on cancer and rare diseases.
• To detail therapeutic strategies targeting cancer through modulation of ribosome biogenesis.

Main Methods:

• Review of current scientific literature on ribosome biogenesis, cancer, and rare diseases.
• Analysis of in vitro and in vivo studies on therapeutic chemical entities.
• Discussion of potential therapeutic targets and strategies.

Main Results:

• Impaired ribosome biogenesis affects protein synthesis, transcriptional/translational responses, and metabolic pathways.
• Therapeutic modulation of ribosome biogenesis shows promise in preclinical cancer models.
• Specific targets include oncoprotein translation, ribosome assembly, ribosomal stress, and ribosomal function rewiring.

Conclusions:

• Despite established links between inherited ribosome biogenesis defects and cancer, targeted therapies are emerging.
• Developing new chemical entities to modulate ribosome biogenesis checkpoints is a promising strategy.
• Repurposing existing drugs, alone or in combination, warrants consideration for clinical trials due to known safety profiles and potential synergistic effects.