Abstract
Ribosome biogenesis is a complex process that is responsible for the formation of ribosomes and ultimately global protein synthesis. The first step in this process is the synthesis of the ribosomal RNA in the nucleolus, transcribed by RNA Polymerase I. Historically, abnormal nucleolar structure is indicative of poor cancer prognoses. In recent years, it has been shown that ribosome biogenesis, and rDNA transcription in particular, is dysregulated in cancer cells. Coupled with advancements in screening technology that allowed for the discovery of novel drugs targeting RNA Polymerase I, this transcriptional machinery is an increasingly viable target for cancer therapies. In this review, we discuss ribosome biogenesis in breast cancer and the different cellular pathways involved. Moreover, we discuss current therapeutics that have been found to affect rDNA transcription and more novel drugs that target rDNA transcription machinery as a promising avenue for breast cancer treatment.
Highlights
According to the presence/absence of estrogen or progesterone receptors (ER, PR), and amplification of human epidermal growth factor receptor 2 (HER-2, encoded by ERBB2), Breast Cancer. GenesBreast cancer (BC) is categorized into three main subtypes: ER+PR+/HER2− (70%), HER+ (15–20%), and triple-negative (15%, TNBC) [4]
Ribosome biogenesis (RiBi) has become a promising strategy in BC treatment, and ribosomal RNA (rRNA) transcription, the initial step of RiBi has become the main focus
Since rDNA transcription drives nucleolar formation and is the rate limiting step for cellular proliferation, advances in our understanding of molecules and pathways involved in controlling RNAPI activity will lead to new insights into the pathogenetic mechanisms underlying breast cancer tumorigenesis
Summary
Breast cancer (BC) has become a global health burden with the second highest incidence in combined sexes—it is the most frequent malignancy in women. Experts believe the global incidence and mortality rates will keep increasing in the few years, marking a need for continued research on BC and treatment options [2]. There is still an urgent need for new therapeutic strategies in treating BC, especially for TNBC and metastatic. 1896 [8], which put forward the connection between malignancy and nucleoli, the main cellular location for ribosomal RNA (rRNA) synthesis. RiBi has become a promising strategy in BC treatment, and rRNA transcription, the initial step of RiBi has become the main focus. Polymerase I (RNAPI) transcription, and further discuss the different signal transduction pathways that modulate RNAPI activity We discuss both the new and old drugs targeting rRNA synthesis that have potential application in BC treatment
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