Anticancer drug development against ribosome synthesis and the nucleolus.

Abstract

Nucleoli, the most prominent nuclear organelle, form around ribosomal DNA (rDNA) clusters at the p-arms of the five acrocentric chromosomes. Nucleoli are centers of ribosome synthesis, a vital activity in cell proliferation and organism viability. Ribosome biogenesis is a complex process involving the activity of all three RNA polymerases and numerous cellular factors. This energy-consuming process is, therefore, highly regulated, with the transcription of rDNA being the rate-limiting step. Given that uncontrolled cell proliferation is a hallmark of cancer, enhanced ribosome biogenesis plays a crucial role in sustaining tumor growth. In addition, nucleoli are multi-functional organelles, participating in genome organization, cell cycle, stress sensing, macromolecular trafficking, and the sequestration of cellular factors-functions that are also significantly altered in cancerous conditions. This review focuses on summarizing the role of nucleoli in carcinogenesis and anticancer therapeutics that target nucleoli and ribosome synthesis.