Alterations in Ribosome Structure, Integrity and Function in Cancer and in Response to Cancer Treatments

Dear Colleagues,

Research on ribosomes and the mechanisms of ribosome dysfunction in diseases including carcinogenesis is expanding rapidly. Accordingly, it is very timely that a joint Special Issue of Cancers and the Journal of Personalized Medicine will be focused on Ribosomes, Cancer and Personalized Medicine.

Protein translation by ribosomes is one of the most energetically costly processes in cells. Thus, ribosome production, assembly, composition, integrity and activity are highly regulated in cells and strongly reduced in response to stress [1–3]. Ribosomes from tumour cells differ in sequence and function from normal cells. For example, such “oncoribosomes” have highly enhanced translational capacity to support tumour cell replication and invasion [4,5]. Therefore, it is not surprising that the oncoribosome is increasingly being seen as an attractive anti-cancer target and a variety of clinical trials are underway, assessing the efficacy of drugs that inhibit protein translation [6,7]. Recently, it has been shown that a variety of stresses including diverse chemotherapy agents can induce ribosomal RNA degradation in tumour cells, a phenomenon termed as “RNA disruption” [8]. The immune cell-mediated destruction of tumour cells is also associated with strong RNA disruption [9]. Clinical studies have shown that high RNA disruption during neoadjuvant chemotherapy in breast cancer patients is associated with pathologic complete response and improved survival post-treatment [10], while low RNA disruption is associated with poor outcome [11].

Papers on the above topics as well as on ribosome evolution, synthesis, turnover and degradation with a specific focus on neoplasia are welcome, as are papers that consider the possible future ribosomal roles in personalized medicine, i.e., future individualized cancer diagnosis and therapy.

1. Shcherbik, N.; Pestov, D.G. The Impact of Oxidative Stress on Ribosomes: From Injury to Regulation. Cells 2019, 8, 1379. https://doi.org/10.3390/cells8111379.
2. Kazibwe, Z.; Liu, A.-Y.; MacIntosh, G.C.; Bassham, D.C. The Ins and Outs of Autophagic Ribosome Turnover. Cells 2019, 8, 1603. https://doi.org/10.3390/cells8121603.
3. Pirogov, S.A.; Gvozdev, V.A.; Klenov, M.S. Long Noncoding RNAs and Stress Response in the Nucleolus. Cells 2019, 8, 668. https://doi.org/10.3390/cells8070668.
4. Kampen, K.R.; O Sulima, S.; Vereecke, S.; De Keersmaecker, K. Hallmarks of ribosomopathies. Nucleic Acids Res. 2019, 48, 1013–1028, https://doi.org/10.1093/nar/gkz637.
5. Babaian, A.; Rothe, K.; Girodat, D.; Minia, I.; Djondovic, S.; Milek, M.; Miko, S.E.S.; Wieden, H.-J.; Landthaler, M.; Morin, G.B.; et al. Loss of m1acp3Ψ Ribosomal RNA Modification Is a Major Feature of Cancer. Cell Rep. 2020, 31, 107611. https://doi.org/10.1016/j.celrep.2020.107611.
6. Zisi, A.; Bartek, J.; Lindström, M.S. Targeting Ribosome Biogenesis in Cancer: Lessons Learned and Way Forward. Cancers 2022, 14, 2126. https://doi.org/10.3390/cancers14092126.
7. Gilles, A.; Frechin, L.; Natchiar, K.; Biondani, G.; von Loeffelholz, O.; Holvec, S.; Malaval, J.-L.; Winum, J.-Y.; Klaholz, B.P.; Peyron, J.-F. Targeting the Human 80S Ribosome in Cancer: From Structure to Function and Drug Design for Innovative Adjuvant Therapeutic Strategies. Cells 2020, 9, 629. https://doi.org/10.3390/cells9030629.
8. Butler, P.; Pascheto, I.; Lizzi, M.; St-Onge, R.; Lanner, C.; Guo, B.; Masilamani, T.; Pritzker, L.B.; Kovala, A.T.; Parissenti, A.M. RNA disruption is a widespread phenomenon associated with stress-induced cell death in tumour cells. Sci. Rep. 2023, 13, 1–16. https://doi.org/10.1038/s41598-023-28635-8.
9. Kong, C.K.; Low, L.E.; Siew, W.S.; Yap, W.H.; Khaw, K.Y.; Ming, L.C.; Mocan, A.; Goh, B.H.; Goh, P.H. Biological activities of snowdrop (Galanthus spp., Family Amaryllidaceae). Front. Pharmacol. 2021, 11, 552453. https://doi.org/10.3389/fphar.2020.552453
10. Parissenti, A.M.; Guo, B.; Pritzker, L.B.; Pritzker, K.P.H.; Wang, X.; Zhu, M.; Shepherd, L.E.; Trudeau, M.E. Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy. Breast Cancer Res. Treat. 2015, 153, 135–144. https://doi.org/10.1007/s10549-015-3498-9.
11. Cazzaniga, M.E.; Ademuyiwa, F.; Petit, T.; Tio, J.; Generali, D.; Ciruelos, E.M.; Califaretti, N.; Poirier, B.; Ardizzoia, A.; Hoenig, A.; et al. Low RNA disruption during neoadjuvant chemotherapy predicts pathologic complete response absence in patients with breast cancer. JNCI Cancer Spectr. 2023, 8. https://doi.org/10.1093/jncics/pkad107.

You may choose our Joint Special Issue in JPM.

Prof. Dr. Amadeo Mark Parissenti
Prof. Dr. Kenneth Pritzker
Guest Editors

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• ribosome
• protein translation
• ribosome evolution
• ribosome modification
• oncoribosome
• ribosomal anti-cancer targets
• stress
• ribosome turnover
• ribosomal RNA (rRNA)
• rRNA degradation pathways
• tumour cell death
• clinical trials
• chemotherapy
• predictive and prognostic biomarkers
• personalized medicine