Inhibition of the serine/threonine kinase BUB1 reverses taxane resistance in prostate cancer

Martinez, Maria J.; Lyles, Rolando D.Z.; Peinetti, Nahuel; Grunfeld, Alex M.; Burnstein, Kerry L.

doi:10.1016/j.isci.2023.107681

Cited by 4 publications

(1 citation statement)

References 64 publications

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“…Thus, enhancing the CIN level has been proposed as a promising approach to target tumor cells, and strategies to exacerbate CIN for anti-tumor therapy have been explored. 66,358,406,[409][410][411][412][413][414][415][416][417][418][419][420][421][422] For example, taxol could increase the number and severity of chromosome segregation errors in tumor cells, while cells with excessive CIN were more sensitive to low doses of taxol. 423 Indeed, combining taxol and monopolar spindle 1 (MPS1) inhibitor could reduce xenograft growth more effectively than either compound alone.…”

Section: Cin Paradoxmentioning

confidence: 99%

The two sides of chromosomal instability: drivers and brakes in cancer

Hosea,

Hillary,

Naqvi

et al. 2024

Sig Transduct Target Ther

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Chromosomal instability (CIN) is a hallmark of cancer and is associated with tumor cell malignancy. CIN triggers a chain reaction in cells leading to chromosomal abnormalities, including deviations from the normal chromosome number or structural changes in chromosomes. CIN arises from errors in DNA replication and chromosome segregation during cell division, leading to the formation of cells with abnormal number and/or structure of chromosomes. Errors in DNA replication result from abnormal replication licensing as well as replication stress, such as double-strand breaks and stalled replication forks; meanwhile, errors in chromosome segregation stem from defects in chromosome segregation machinery, including centrosome amplification, erroneous microtubule–kinetochore attachments, spindle assembly checkpoint, or defective sister chromatids cohesion. In normal cells, CIN is deleterious and is associated with DNA damage, proteotoxic stress, metabolic alteration, cell cycle arrest, and senescence. Paradoxically, despite these negative consequences, CIN is one of the hallmarks of cancer found in over 90% of solid tumors and in blood cancers. Furthermore, CIN could endow tumors with enhanced adaptation capabilities due to increased intratumor heterogeneity, thereby facilitating adaptive resistance to therapies; however, excessive CIN could induce tumor cells death, leading to the “just-right” model for CIN in tumors. Elucidating the complex nature of CIN is crucial for understanding the dynamics of tumorigenesis and for developing effective anti-tumor treatments. This review provides an overview of causes and consequences of CIN, as well as the paradox of CIN, a phenomenon that continues to perplex researchers. Finally, this review explores the potential of CIN-based anti-tumor therapy.

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Section: Cin Paradoxmentioning

confidence: 99%

The two sides of chromosomal instability: drivers and brakes in cancer

Hosea,

Hillary,

Naqvi

et al. 2024

Sig Transduct Target Ther

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The yin and yang of chromosomal instability in prostate cancer

Carceles-Cordon,

Orme,

Domingo-Domenech

et al. 2024

Nat Rev Urol

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Expression of the checkpoint kinase BUB1 is a predictor of response to cancer therapies

Cicirò,

Ragusa,

Sala

2024

Sci Rep

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The identification of clinically-relevant biomarkers is of upmost importance for the management of cancer, from diagnosis to treatment choices. We performed a pan-cancer analysis of the mitotic checkpoint budding uninhibited by benzimidazole 1 gene BUB1, in the attempt to ascertain its diagnostic and prognostic values, specifically in the context of drug response. BUB1 was found to be overexpressed in the majority of cancers, and particularly elevated in clinically aggressive molecular subtypes. Its expression was correlated with clinico-phenotypic features, notably tumour staging, size, invasion, hypoxia, and stemness. In terms of prognostic value, the expression of BUB1 bore differential clinical outcomes depending on the treatment administered in TCGA cancer cohorts, suggesting sensitivity or resistance, depending on the expression levels. We also integrated in vitro drug sensitivity data from public projects based on correlation between drug efficacy and BUB1 expression to produce a list of candidate compounds with differential responses according to BUB1 levels. Gene Ontology enrichment analyses revealed that BUB1 overexpression in cancer is associated with biological processes related to mitosis and chromosome segregation machinery, reflecting the mechanisms of action of drugs with a differential effect based on BUB1 expression.

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Inhibition of the serine/threonine kinase BUB1 reverses taxane resistance in prostate cancer

Cited by 4 publications

References 64 publications

The two sides of chromosomal instability: drivers and brakes in cancer

The two sides of chromosomal instability: drivers and brakes in cancer

The yin and yang of chromosomal instability in prostate cancer

Expression of the checkpoint kinase BUB1 is a predictor of response to cancer therapies

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