Ribosome biogenesis pathway (RiBi)

Ribosome biogenesis is the essential cellular process of synthesizing ribosomes, involving the transcription of ribosomal DNA (rDNA) into precursor ribosomal RNA (rRNA), its processing, and assembly with ribosomal proteins. In cancer cells, this pathway is constitutively upregulated to support the high protein synthesis rates required for rapid proliferation and survival (Nature Reviews Cancer, 2019). This hyperactivation is often mediated by oncogenic signaling pathways, such as the MYC and mTOR pathways, which directly stimulate RNA Polymerase I (Pol I) activity. Therapeutic targeting of the ribosome biogenesis pathway primarily focuses on inhibiting Pol I-mediated transcription of the 45S pre-rRNA. Disruption of this process leads to nucleolar stress, characterized by the redistribution of nucleolar proteins like nucleophosmin (NPM1) and the stabilization of the tumor suppressor p53 (Cell Death & Differentiation, 2018). Small molecules like CX-5461 (Pidnarulex) and BMH-21 have been developed to selectively target Pol I, showing efficacy in various hematologic and solid tumors. Because malignant cells are more dependent on accelerated ribosome production than normal cells, they exhibit a greater sensitivity to these inhibitors, providing a therapeutic window. Beyond Pol I inhibition, other drugs like oxaliplatin also exert part of their anti-tumor activity by interfering with rRNA processing (Nature Communications, 2017). Monitoring nucleolar morphology and rRNA synthesis levels serves as a potential biomarker for assessing the efficacy of these treatments.

Other names

Ribosome synthesisrRNA synthesis and processingNucleolar stress response pathwayRibosomal biogenesis

Inhibition of RNA Polymerase I-mediated transcription of ribosomal DNA (rDNA), leading to nucleolar stress and subsequent activation of tumor suppressor pathways such as p53.