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Open AccessReview

Therapeutic Approaches Targeting Nucleolus in Cancer

1
The Institute of Cancer Research, Cancer Therapeutic Unit, London SM2 5NG, UK
2
Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli 80078, Italy
3
Department of Pharmacy, School of Medicine, University of Naples Federico II, Via Domenico Montesano 49, 80131 Naples, Italy
4
Department of Advanced Biomedical Science, School of Medicine, University of Naples Federico II, 80131 Naples, Italy
*
Authors to whom correspondence should be addressed.
Cells 2019, 8(9), 1090; https://doi.org/10.3390/cells8091090
Received: 12 August 2019 / Revised: 8 September 2019 / Accepted: 13 September 2019 / Published: 16 September 2019
(This article belongs to the Special Issue Nucleolar Organization and Functions in Health and Disease)
The nucleolus is a distinct sub-cellular compartment structure in the nucleus. First observed more than 200 years ago, the nucleolus is detectable by microscopy in eukaryotic cells and visible during the interphase as a sub-nuclear structure immersed in the nucleoplasm, from which it is not separated from any membrane. A huge number of studies, spanning over a century, have identified ribosome biogenesis as the main function of the nucleolus. Recently, novel functions, independent from ribosome biogenesis, have been proposed by several proteomic, genomic, and functional studies. Several works have confirmed the non-canonical role for nucleoli in regulating important cellular processes including genome stability, cell-cycle control, the cellular senescence, stress responses, and biogenesis of ribonucleoprotein particles (RNPs). Many authors have shown that both canonical and non-canonical functions of the nucleolus are associated with several cancer-related processes. The association between the nucleolus and cancer, first proposed by cytological and histopathological studies showing that the number and shape of nucleoli are commonly altered in almost any type of cancer, has been confirmed at the molecular level by several authors who demonstrated that numerous mechanisms occurring in the nucleolus are altered in tumors. Recently, therapeutic approaches targeting the nucleolus in cancer have started to be considered as an emerging “hallmark” of cancer and several therapeutic interventions have been developed. This review proposes an up-to-date overview of available strategies targeting the nucleolus, focusing on novel targeted therapeutic approaches. Finally, a target-based classification of currently available treatment will be proposed. View Full-Text
Keywords: nucleolar stress; p53; ribosomal proteins; cancer; uL3; cancer chemotherapy; nucleolus nucleolar stress; p53; ribosomal proteins; cancer; uL3; cancer chemotherapy; nucleolus
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Carotenuto, P.; Pecoraro, A.; Palma, G.; Russo, G.; Russo, A. Therapeutic Approaches Targeting Nucleolus in Cancer. Cells 2019, 8, 1090.

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