Ribosome Biogenesis and Function in Cancer: From Mechanisms to Therapy

Ribosome biogenesis is a highly coordinated, multi-step process that assembles the ribosomal machinery responsible for translating mRNAs into proteins. It begins with the rate-limiting step of RNA polymerase I (Pol I) transcription of the 47S ribosomal RNA (rRNA) genes within a specialised nucleolar region in the nucleus, followed by rRNA processing, modification, and assembly with ribosomal proteins and the 5S rRNA produced by Pol III. The ribosomal subunits are then exported to the cytoplasm to form functional ribosomes. This process is tightly regulated by the PI3K/RAS/MYC oncogenic network, which is frequently deregulated in many cancers. As a result, ribosome synthesis, mRNA translation, and protein synthesis rates are increased. Growing evidence supports the notion that dysregulation of ribosome biogenesis and mRNA translation plays a pivotal role in the pathogenesis of cancer, positioning the ribosome as a promising therapeutic target. In this review, we summarise current understanding of dysregulated ribosome biogenesis and function in cancer, evaluate the clinical development of ribosome targeting therapies, and explore emerging targets for therapeutic intervention in this rapidly evolving field.