ArticleMolecular oncology2016
Chk1 phosphorylated at serine345 is a predictor of early local recurrence and radio-resistance in breast cancer.
Article in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- ATR inhibition potentiates the antitumor efficacy of HER3-DXd in HER3-positive/HR-positive breast cancer by increasing DNA damage.British journal of cancer · 2026Article
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- Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.Frontiers of medicine · 2025Review
- Unravelling the clinicopathological and functional significance of replication protein A (RPA) heterotrimeric complex in breast cancers.NPJ breast cancer · 2023Article
- Nuclear pCHK1 as a potential biomarker of increased sensitivity to ATR inhibition.The Journal of pathology · 2023Article
- Aspirin Restores Radiosensitivity in Cervical Cancer Cells by Inducing Mitotic Catastrophe through Downregulating G2/M Effectors.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Identification of prognostic indicators, diagnostic markers, and possible therapeutic targets among LIM homeobox transcription factors in breast cancer.Cancer innovation · 2022Article
- Radiotherapy resistance: identifying universal biomarkers for various human cancers.Journal of cancer research and clinical oncology · 2022Review
- Untangling the clinicopathological significance of MRE11-RAD50-NBS1 complex in sporadic breast cancers.NPJ breast cancer · 2021Article
- Article
- Understanding the Radiobiology of Vestibular Schwannomas to Overcome Radiation Resistance.Cancers · 2021Review
- Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents.Signal transduction and targeted therapy · 2021Review
- Progress towards a clinically-successful ATR inhibitor for cancer therapy.Current research in pharmacology and drug discovery · 2021Review
- A novel methylation signature predicts radiotherapy sensitivity in glioma.Scientific reports · 2020Article
- How Different Are the Molecular Mechanisms of Nodal and Distant Metastasis in Luminal A Breast Cancer?Cancers · 2020Article
- DNA damage repair functions and targeted treatment in breast cancer.Breast cancer (Tokyo, Japan) · 2020Review
- Reprogramming of Energy Metabolism in Response to Radiotherapy in Head and Neck Squamous Cell Carcinoma.Cancers · 2019Review
- Emerging biomarkers for the combination of radiotherapy and immune checkpoint blockers.Seminars in cancer biology · 2018Review
- The Impact of p53 Dysfunction in ATR Inhibitor Cytotoxicity and Chemo- and Radiosensitisation.Cancers · 2018Article
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Radiation-induced DNA damage activates the DNA damage response (DDR). DDR up-regulation may predict radio-resistance and increase the risk of early local recurrence despite radiotherapy in early stage breast cancers. In 1755 early stage breast cancers, DDR signalling [ATM, ATR, total Ckh1, Chk1 phosphorylated at serine(345) (pChk1), Chk2, p53], base excision repair [PARP1, POLβ, XRCC1, FEN1, SMUG1], non-homologous end joining (Ku70/Ku80, DNA-PKcs) and homologous recombination [RAD51, BRCA1, γH2AX, BLM, WRN, RECQL5, PTEN] protein expression was correlated to time to early local recurrence. Pre-clinically, radio-sensitization by inhibition of Chk1 activation by ATR inhibitor (VE-821) and inhibition of Chk1 (V158411) were investigated in MDA-MB-231 (p53 mutant) and MCF-7 (p53 wild-type) breast cancer cells. In the whole cohort, 208/1755 patients (11.9%) developed local recurrence of which 126 (61%) developed local recurrence within 5 years of initiation of primary therapy. Of the 20 markers tested, only pChk1 and p53 significantly associated with early local recurrence (p value = 0.015 and 0.010, respectively). When analysed together, high cytoplasmic pChk1-nuclear pChk1 (p = 0.039), high cytoplasmic pChk1-p53 (p = 0.004) and high nuclear pChk1-p53 (p = 0.029) co-expression remain significantly linked to early local recurrence. In multivariate analysis, cytoplasmic pChk1 level independently predicted early local recurrence (p = 0.025). In patients who received adjuvant local radiotherapy (n = 949), p53 (p = 0.014) and high cytoplasmic pChk1-p53 (p = 0.017) remain associated with early local recurrence. Pre-clinically, radio-sensitisation by VE-821 or V158411 was observed in both MCF-7 and MDA-MB-231 cells and was more pronounced in MCF-7 cells. We conclude that pChk1 is a predictive biomarker of radiotherapy resistance and early local recurrence.
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