Karyotypic Aberrations in Oncogenesis and Cancer Therapy
Abstract
The propagation of whole-chromosome (aneuploid) or whole-genome (polyploid) defects is normally prevented by robust cell-intrinsic mechanisms. Moreover, non-diploid cells are under strict immunological surveillance. Nonetheless, tumors contain a high percentage of non-diploid genomes, indicating that malignant cells acquire the ability to bypass these control mechanisms and obtain a survival/proliferation benefit from bulky karyotypic defects. The non-diploid state imposes a significant metabolic burden on cancer cells and hence can be selectively targeted for therapeutic purposes. Here we discuss the impact of abnormal karyotypes on oncogenesis, tumor progression, and response to treatment, focusing on the biochemical and metabolic liabilities of non-diploid cells that can be harnessed for the development of novel chemo(immuno)therapeutic regimens against cancer.
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Entotic invasion has been suggested to favor aneuploidization and polyploidization through cytokinesis failure of engulfing cells.
“entotic invasion has also been suggested to favor aneuploidization and polyploidization (which promote tumor progression) [711–713] through a mechanism involving cytokinesis failure of engulfing cells [714, 715].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [713]
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Musacchio, A., & Ciliberto, A. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2429 · Cited by 30 · see citing works
Tetraploidization increases sensitivity to Aurora B kinase inhibition
Marxer, M., Foucar, C. E., Man, W. Y., Chen, Y., Ma, H. T., & Poon, R. Y. C. (2012) · Cell Cycle · doi:10.4161/cc.20947 · Cited by 24 · see citing works
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Sarcoid-derived fibroblasts: Links between genomic instability, energy metabolism and senescence
Potocki, L., Lewińska, A., Klukowska‐Rötzler, J., Bielak-Żmijewska, A., Grabowska, W., Rzeszutek, I., Kaminska, P., Roga, E., Bugno‐Poniewierska, M., Słota, E., et al. (2013) · Biochimie · doi:10.1016/j.biochi.2013.10.010 · Cited by 21 · see citing works
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Flagged first, then by citations
1 of the 96 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Self-citationIntratumoral heterogeneity in cancer progression and response to immunotherapy
Vitale, I., Shema, E., Loi, S., & Galluzzi, L. (2021) · Nature Medicine · doi:10.1038/s41591-021-01233-9 · Cited by 823 · see citing works
Self-citationLinking cellular stress responses to systemic homeostasis
Galluzzi, L., Yamazaki, T., & Kroemer, G. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0068-0 · Cited by 529 · see citing works
Self-citationMechanisms of Regulated Cell Death: Current Perspectives
Santagostino, S. F., Assenmacher, C., Tarrant, J. C., Adedeji, A. O., & Radaelli, E. (2021) · Veterinary Pathology · doi:10.1177/03009858211005537 · Cited by 133 · see citing works
Manic, G., Signore, M., Sistigu, A., Russo, G., Corradi, F., Siteni, S., Musella, M., Vitale, S., De Angelis, M. L., Pallocca, M., et al. (2018) · Gut · doi:10.1136/gutjnl-2016-312623 · Cited by 98 · see citing works
Self-citationMutational and Antigenic Landscape in Tumor Progression and Cancer Immunotherapy
Vitale, I., Sistigu, A., Manic, G., Rudqvist, N.-P., Trajanoski, Z., & Galluzzi, L. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.01.003 · Cited by 94 · see citing works
Self-citationDifference Makers: Chromosomal Instability versus Aneuploidy in Cancer
van Jaarsveld, R. H., & Kops, G. J. P. L. (2016) · Trends in cancer · doi:10.1016/j.trecan.2016.09.003 · Cited by 70 · see citing works
“For a more elaborated view on aneuploidy as a therapeutic target, we refer interested readers to an excellent recent review [96].”
BackgroundEmerging biomarkers for the combination of radiotherapy and immune checkpoint blockers
Lhuillier, C., Vanpouille‐Box, C., Galluzzi, L., Formenti, S. C., & Demaria, S. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.12.007 · Cited by 62 · see citing works
Self-citationMolecular Regulation of the Spindle Assembly Checkpoint by Kinases and Phosphatases
Manic, G., Corradi, F., Sistigu, A., Siteni, S., & Vitale, I. (2016) · International review of cytology · doi:10.1016/bs.ircmb.2016.08.004 · Cited by 53 · see citing works
Self-citationMitotic checkpoint defects: en route to cancer and drug resistance
Sarkar, S., Sahoo, P. K., Mahata, S., Pal, R., Ghosh, D., Mistry, T., Ghosh, S., Bera, T., & Nasare, V. D. (2021) · Chromosome Research · doi:10.1007/s10577-020-09646-x · Cited by 53 · see citing works
Gerstein, A. C., Lim, H., Berman, J. G., & Hickman, M. A. (2017) · Evolution · doi:10.1111/evo.13205 · Cited by 43 · see citing works
Replication stress response in cancer stem cells as a target for chemotherapy
Manic, G., Sistigu, A., Corradi, F., Musella, M., Maria, R. D., & Vitale, I. (2018) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2018.08.003 · Cited by 43 · see citing works
Self-citationCaspase 2 in mitotic catastrophe: The terminator of aneuploid and tetraploid cells
Vitale, I., Manic, G., Castedo, M., & Kroemer, G. (2017) · Molecular & Cellular Oncology · doi:10.1080/23723556.2017.1299274 · Cited by 31 · see citing works
“alterations, the most frequent of which are aneuploidy (an unbalanced state arising from the mis-segregation of one or more chromosomes) and tetraploidy (an aberrant form of euploidy resulting from one round of whole-genome doubling); and (2) chromosomal instability (CIN), a condition characterized by the inability to…”
BackgroundSelf-citationTrial watch: DNA-based vaccines for oncological indications
Pierini, S., Perales-Linares, R. F., Uribe‐Herranz, M., Pol, J. G., Zitvogel, L., Kroemer, G., Facciabene, A., & Galluzzi, L. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1398878 · Cited by 30 · see citing works
Self-citationPolyploidy mitigates the impact of DNA damage while simultaneously bearing its burden
Hayashi, K., Horisaka, K., Harada, Y., Ogawa, Y., Yamashita, T., Kitano, T., Wakita, M., Fukusumi, T., Inohara, H., Hara, E., et al. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02206-w · Cited by 24 · see citing works
“Among the conditions involving dynamic ploidy alterations, the importance of polyploidization in cancer has been relatively well examined [7, 8].”
BackgroundSemaan, A., Bernard, V., Lee, J. J., Wong, J., Huang, J. H., Swartzlander, D. B., Stephens, B. M., Monberg, M. E., Weston, B. R., Bhutani, M. S., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2667 · Cited by 24 · see citing works
“In this regard, tumors with high aneuploidy have shown increased tumor progression and chemotherapy resistance due to a higher intratumoral heterogeneity and ultimately an elevated capacity for adaptation (52).”
BackgroundImmunosurveillance of Malignant Cells with Complex Karyotypes
López‐Soto, A., Gonzalez, S. R., López‐Larrea, C., & Kroemer, G. (2017) · Trends in Cell Biology · doi:10.1016/j.tcb.2017.09.001 · Cited by 16 · see citing works
Self-citationHIPK2 and extrachromosomal histone H2B are separately recruited by Aurora-B for cytokinesis
Monteonofrio, L., Valente, D., Ferrara, M., Camerini, S., Miscione, R., Crescenzi, M., Rinaldo, C., & Soddu, S. (2018) · Oncogene · doi:10.1038/s41388-018-0191-6 · Cited by 16 · see citing works
Tetraploidization Increases the Motility and Invasiveness of Cancer Cells
Jèmaà, M., Daams, R., Charfi, S., Mertens, F., Huber, S. M., & Massoumi, R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813926 · Cited by 13 · see citing works
“The resulting viable aneuploid cells drive tumorigenesis as they are resistant to apoptosis and show enhanced proliferation and metastasis [4,6,7].”
BackgroundTargeting cytokinesis bridge proteins to kill high-CIN type tumors
Xie, B., Liang, X., Yue, W., Ma, J., Li, X., Zhang, N., Wang, P., Liu, C., Shi, X., Qiao, J., et al. (2021) · Fundamental Research · doi:10.1016/j.fmre.2021.08.015 · Cited by 10 · see citing works
Catastrophic DNA replication in unscheduled tetraploid cells
Manic, G., Galluzzi, L., & Vitale, I. (2022) · Trends in Genetics · doi:10.1016/j.tig.2022.04.005 · Cited by 10 · see citing works
Self-citationImpact of the ECM on the Mechanical Memory of Cancer Cells
Mierke, C. T. (2025) · Cells · doi:10.3390/cells14211707 · Cited by 9 · see citing works
Ploidy Status of Ovarian Cancer Cell Lines and Their Association with Gene Expression Profiles
Du, M., Zhang, S., Liu, X., Xu, C., & Zhang, X. (2023) · Biomolecules · doi:10.3390/biom13010092 · Cited by 9 · see citing works
“Nondiploid cells are different from diploid cells in terms of cell fitness and characteristics, featuring worse genomic, metabolic, proteotoxic stress and immune stress, manifested as senescence and cell cycle arrest [49,50].”
BackgroundChromatin and genomic instability in cancer
Weyemi, U., & Galluzzi, L. (2021) · International review of cytology · doi:10.1016/s1937-6448(21)00116-7 · Cited by 9 · see citing works
Self-citationSpontaneous DNA damage propels tumorigenicity
Vitale, I., & Kroemer, G. (2017) · Cell Research · doi:10.1038/cr.2017.43 · Cited by 6 · see citing works
Self-citationDriving to Cancer on a Four-Lane Expressway
Galluzzi, L., & Vitale, I. (2017) · Trends in Genetics · doi:10.1016/j.tig.2017.06.003 · Cited by 6 · see citing works
Self-citationJèmaà, M., Boubaker, N. S., Kerkeni, N., & Huber, S. M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26031209 · Cited by 5 · see citing works
“Except in certain physiological states, cells do not tolerate tetraploidy and activate programmed death pathways leading to their elimination [1,2].”
Cancer memory as a mechanism to establish malignancy
Lissek, T. (2024) · Biosystems · doi:10.1016/j.biosystems.2024.105381 · Cited by 4 · see citing works
Everybody In! No Bouncers at Tumor Gates
Vitale, I., & Galluzzi, L. (2017) · Trends in Genetics · doi:10.1016/j.tig.2017.12.006 · Cited by 3 · see citing works
Self-citationSynchronization and Desynchronization of Cells by Interventions on the Spindle Assembly Checkpoint
Jèmaà, M., Manic, G., & Vitale, I. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-6603-5_5 · Cited by 2 · see citing works
Self-citationWang, Y., Lin, A. Y., Wang, D. D., Lin, P. P., Zhou, X., Yang, Y., & Zhu, Y. (2025) · BMC Cancer · doi:10.1186/s12885-025-14346-y · Cited by 1 · see citing works
“The diagnostic role of aneuploid TECs is not remarkable, whereas the presence of aneuploid TECs is crucial for antiangiogenic therapy, as chromosomal instability may provide a mechanism to alter endothelial cells and render them resistant to drugs [46, 47].”
Maladaptation diseases as disorders of intraorganismal individuation
Lissek, T. (2025) · Biosystems · doi:10.1016/j.biosystems.2025.105621 · Cited by 1 · see citing works
Replication stress in colorectal cancer stem cells
Manic, G., Maria, R. D., & Vitale, I. (2017) · Oncotarget · doi:10.18632/oncotarget.18045 · Cited by 1 · see citing works
Self-citationSemaan, A., Bernard, V., Lee, J. J., Wong, J., Huang, J. H., Swartzlander, D. B., Stephens, B. M., Monberg, M. E., Weston, B. R., Bhutani, M. S., et al. (2023) · doi:10.1158/1078-0432.c.6530151
- Authors
- Vitale, I., Manic, G., Senovilla, L., Kroemer, G., & Galluzzi, L.
- Affiliations
- University of Rome Tor Vergata (IT)
- Instituto Nazionale Tumori Regina Elena (IT)
- Inserm (FR)
- Karolinska University Hospital (SE)
- Corresponding author
- Galluzzi, Lorenzo
- Venue
- Trends in Cancer
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 1
- Issue
- 2
- Pages
- 124-135
- ISSN
- 2405-8025 (ISSN-L)
- 2405-8033
- OpenAlex
- W1863134146
- Cited by
- 34
- References
- 96
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 10 · 2016: 3
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- aneuploidy, polyploidy, carcinogenesis, tumor progression, cancer therapy, cancer metabolism, metabolic liability, tumor surveillance, chemoimmunotherapy
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