ArticleThe Journal of clinical investigation2020
TTK inhibition radiosensitizes basal-like breast cancer through impaired homologous recombination.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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The trial behind it
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Who cites it
53 citing papers in PubMed, 83 citations in OpenAlex.
- Expanding Synthetic Lethality in DNA Damage Response-Defective Cancers Through Stress Phenotype-Guided Kinase Targeting.International journal of molecular sciences · 2026Review
- BUB1 and CDK4/6 Dual Inhibition Increases Radiation Sensitivity in Glioblastoma, Lung Cancer, and Triple-Negative Breast Cancer.Biomedicines · 2026Article
- Pretreatment Chromosomal Instability Correlates With Radiation Sensitivity in Squamous Cell Cancers.International journal of radiation oncology, biology, physics · 2026Article
- Genetically predicted TTK inhibition and its association with reduced breast cancer risk: a two-step Mendelian randomization study of potential gut microbiome mediation.Clinics (Sao Paulo, Brazil) · 2026Article
- Developing a gene expression classifier for breast cancer diagnosis.Medical & biological engineering & computing · 2025Article
- Targeting monopolar spindle kinase I (Mps1 or TTK) induces radiosensitization in syngeneic models of triple negative breast cancer (TNBC) and potentiates type I interferon (T1IFN) signaling.Neoplasia (New York, N.Y.) · 2025Article
- PIPKIγ promotes non-homologous end joining through LIG4 to enhance radiotherapy resistance in triple-negative breast cancer.Cell death & disease · 2025Article
- TTK activates ATR through RPA2 phosphorylation to promote olaparib resistance in ovarian cancer.Communications biology · 2025Article
- Article
- Tumor Microenvironment Dynamics of Triple-Negative Breast Cancer Under Radiation Therapy.International journal of molecular sciences · 2025Review
- Machine learning selection of basement membrane-associated genes and development of a predictive model for kidney fibrosis.Scientific reports · 2025Article
- Comparative bioinformatics analysis of the Wnt pathway in breast cancer: Selection of novel biomarker panels associated with ER status.Open life sciences · 2025Article
- Mitotic kinases are emerging therapeutic targets against metastatic breast cancer.Cell division · 2024Review
- BUB1 regulates non-homologous end joining pathway to mediate radioresistance in triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Article
- Upregulation of TTK expression is associated with poor prognosis and immune infiltration in endometrial cancer patients.Cancer cell international · 2024Article
- Dual TTK/PLK1 inhibition has potent anticancer activity in TNBC as monotherapy and in combination.Frontiers in oncology · 2024Article
- Bevacizumab increases the sensitivity of olaparib to homologous recombination-proficient ovarian cancer by suppressing CRY1 via PI3K/AKT pathway.Frontiers in oncology · 2024Article
- Impact of sequencing of androgen receptor-signaling inhibition and radiotherapy in prostate cancer: importance of homologous recombination disruption.World journal of urology · 2023Article
- Patient-derived organoids as personalized avatars and a potential immunotherapy model in cervical cancer.iScience · 2023Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 1 country.
Funding
Abstract
Increased rates of locoregional recurrence are observed in patients with basal-like breast cancer (BC) despite the use of radiation therapy (RT); therefore, approaches that result in radiosensitization of basal-like BC are critically needed. Using patients' tumor gene expression data from 4 independent data sets, we correlated gene expression with recurrence to find genes significantly correlated with early recurrence after RT. The highest-ranked gene, TTK, was most highly expressed in basal-like BC across multiple data sets. Inhibition of TTK by both genetic and pharmacologic methods enhanced radiosensitivity in multiple basal-like cell lines. Radiosensitivity was mediated, at least in part, through persistent DNA damage after treatment with TTK inhibition and RT. Inhibition of TTK impaired homologous recombination (HR) and repair efficiency, but not nonhomologous end-joining, and decreased the formation of Rad51 foci. Reintroduction of wild-type TTK rescued both radioresistance and HR repair efficiency after TTK knockdown; however, reintroduction of kinase-dead TTK did not. In vivo, TTK inhibition combined with RT led to a significant decrease in tumor growth in both heterotopic and orthotopic, including patient-derived xenograft, BC models. These data support the rationale for clinical development of TTK inhibition as a radiosensitizing strategy for patients with basal-like BC, and efforts toward this end are currently underway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.