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    GENE:

    ATR (Ataxia telangiectasia and Rad3-related protein)

    i
    Other names: ATR, ATR Serine/Threonine Kinase, Ataxia Telangiectasia And Rad3-Related Protein, Serine/Threonine-Protein Kinase ATR, FRP1, MEC1, Mitosis Entry Checkpoint 1, Homolog, Ataxia Telangiectasia And Rad3 Related, FRAP-Related Protein-1, SCKL1, MEC1
    7d
    Microenvironmental acidosis drives PARP- and ATM inhibitor resistance in p53 deficient pancreatic cancer. (PubMed, iScience)
    Whereas p53 KO organoids are sensitive to the combined inhibition of ATM and PARP, acid adaptation partially rescues this phenotype, increasing treatment resistance in a manner partially restored by the combined inhibition of pH-regulatory transporters. We conclude that p53 loss rewires acid-base homeostasis and that microenvironment acidity limits treatment response in p53-deficient PDAC, possibly by increasing cancer cell pH homeostasis capacity.
    Journal • PARP Biomarker
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    TP53 (Tumor protein P53) • ATR (Ataxia telangiectasia and Rad3-related protein) • CHEK1 (Checkpoint kinase 1)
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    TP53 mutation
    17d
    Next Generation DNA Damage Response Inhibitors: Harnessing Nanocarriers and Tumor Microenvironment for Precision Cancer Therapy. (PubMed, Oncol Res)
    Lastly, we touch upon the new nanocarrier-based delivery approaches that enhance pharmacokinetics, target resistant tumor niches, and expand the possibilities for combinatorics with immunotherapy and radiotherapy. Collectively, these findings provide a guide to the implementation of next-generation DDR inhibitors and nanomedicines to deliver a more accurate, durable, and context-specific cancer therapy.
    Review • Journal • PARP Biomarker • IO biomarker
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    ATR (Ataxia telangiectasia and Rad3-related protein) • STING (stimulator of interferon response cGAMP interactor 1) • CHEK1 (Checkpoint kinase 1)
    18d
    Physalin A interferes with cell cycle in human oral squamous carcinoma cells via DNA topoisomerase II/ATM/ATR/Chk signaling for G2/M phase arrest. (PubMed, Arch Biochem Biophys)
    In summary, PA binds to human DNA Topoisomerase IIα/β, then induces Topo/ATM/ATR/CHK signaling pathways, which cleave PARP and γ-H2AX, leading to p-p53 activation and cell cycle arrest at the G2/M phase in HSC-3 cells. It is suggested that PA could develop a novel therapeutic agent against OSCC cells in the future.
    Journal • PARP Biomarker
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    CHEK2 (Checkpoint kinase 2) • ATR (Ataxia telangiectasia and Rad3-related protein) • CHEK1 (Checkpoint kinase 1) • CCNA2 (Cyclin A2) • WEE1 (WEE1 G2 Checkpoint Kinase) • CDK1 (Cyclin-dependent kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CAT (Catalase) • PI3K (Phosphoinositide 3-kinases)
    21d
    ZFP161 promotes colorectal cancer progression by transcriptionally activating c-MYC. (PubMed, Front Oncol)
    Furthermore, high ZFP161 expression is associated with poor survival in patients with mixed colon adenocarcinoma. These findings suggest that the regulation of c-MYC by ZFP161 may represent a potential therapeutic target in c-MYC-driven cancers.
    Journal
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ATR (Ataxia telangiectasia and Rad3-related protein)
    22d
    Molecular Effect of Tobacco on Genetic, Epigenetic, and Metabolic Pathways During Cancer Progression. (PubMed, Cureus)
    These findings underscore the need for targeted interventions, such as epigenetic therapies, metabolic reprogramming, and robust tobacco control policies, to mitigate the global burden of tobacco-related diseases. By providing a unified framework for understanding tobacco's molecular impact, this research advocates for precision medicine and public health strategies to address the pervasive effects of tobacco on human health.
    Review • Journal • PARP Biomarker • IO biomarker
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    BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • ATR (Ataxia telangiectasia and Rad3-related protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • MTHFR (Methylenetetrahydrofolate Reductase) • SOX2 • CASP3 (Caspase 3) • POU5F1 (POU Class 5 Homeobox 1) • CASP9 (Caspase 9) • HDAC1 (Histone Deacetylase 1) • YBX1 (Y-Box Binding Protein 1) • NANOG (Nanog Homeobox) • DRD2 (Dopamine Receptor D2) • SUV39H1 (SUV39H1 Histone Lysine Methyltransferase) • TCF4 (Transcription Factor 4) • COMT (Catechol-O-Methyltransferase)
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    TP53 mutation
    1m
    Esophageal Cancer Cells Exhibit Heterogeneity in DNA Double-Strand Break Repair and G2/M Checkpoint Arrest Associated With Cell Viability After Ionizing Radiation. (PubMed, Adv Radiat Oncol)
    Esophageal cancer cell lines with lower capability of RAD51 foci formation exhibited defective DDR and G2/M checkpoint arrest associated with higher radiosensitivity. These findings suggest novel possibilities for predicting the efficacy of DNA damage-inducing cancer therapies, such as chemoradiotherapy, based on DDR proficiency, potentially guiding personalized treatment strategies for esophageal cancer.
    Journal
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    CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • ATR (Ataxia telangiectasia and Rad3-related protein)
    1m
    Analysis of the regulation of model parameters on delay time in the p53 dynamical response to single-stranded breaks. (PubMed, J Bioinform Comput Biol)
    The remaining parameters ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]) all showed a monotonic decrease in sensitivity. This work provides a quantitative blueprint for therapeutic interventions, suggesting that targeting the p53-Mdm2 feedback strength is the most effective strategy to sensitize cancer cells and shorten the critical delay to cell death.
    Journal
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    ATR (Ataxia telangiectasia and Rad3-related protein)
    2ms
    Evaluation of protein expression and oxidative stress index in Duchenne muscular dystrophy. (PubMed, Pediatr Res)
    This study evaluates the expression of DNA damage response genes-ETAA1, TOPBP1, and ATR-in patients with Duchenne Muscular Dystrophy (DMD). The results demonstrate that DMD patients have much greater gene expression levels and oxidative stress indicators than healthy controls. These genes show a favorable correlation with clinical severity indicators such as CKMM, CPK, and LDH. Combining the three markers improves diagnostic sensitivity and specificity, indicating their potential as a multi-gene biomarker panel. The findings shed fresh light on DMD etiology by correlating genomic instability to disease progression and identifying possible molecular targets for early detection and future treatment approaches.
    Journal
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    ATR (Ataxia telangiectasia and Rad3-related protein)
    2ms
    ATR inhibitors: from targeting the DNA damage response to exploiting synthetic lethality-A paradigm shift in Cancer therapy. (PubMed, Bioorg Chem)
    We provide a detailed analysis of the structure-activity relationships (SAR) of leading clinical candidates, including berzosertib, ceralasertib, and elimusertib, focusing on strategic chemical modifications such as scaffold hopping and sulfoximine substitution to optimize selectivity and druggability. Critical challenges, specifically dose-limiting hematological toxicities and acquired resistance, are analyzed alongside the search for robust predictive biomarkers. By synthesizing current pharmacological and clinical data, this work outlines the trajectory for next-generation ATR-targeted precision medicine.
    Review • Journal
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    ATR (Ataxia telangiectasia and Rad3-related protein)
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    berzosertib (M6620) • ceralasertib (AZD6738) • elimusertib (BAY 1895344)
    2ms
    Ex Vivo Immuno-Oncology Platform Reveals Spatial T Cell Infiltration Patterns Linked to ATR Inhibition Responses in High-Grade Serous Ovarian Cancer. (PubMed, Cancer Immunol Res)
    Additionally, the ATRi induced reactivation of CD8+ T cells was linked to spatial interactions with replication stress positive tumor cells. Thus, our iPDC platform presents as a representative high-throughput ex vivo model to advance precision oncology in HGSC uncovering ATRi-immunotherapy combination as a potentially effective therapeutic option for clinical translation.
    Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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    CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • ATR (Ataxia telangiectasia and Rad3-related protein)
    2ms
    Camonsertib, an ATRi, in Combination with Low-Dose Gemcitabine in Solid Tumors with DNA Damage Response (DDR) Aberrations: Preclinical and Phase 1b Results. (PubMed, Clin Cancer Res)
    Camonsertib and low-dose gemcitabine demonstrated preliminary clinical activity, but due to challenging tolerability further evaluation is warranted to identify the optimal dosing regimen and subset of patients who may benefit most from this combination.
    P1 data • Preclinical • Journal
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    ATR (Ataxia telangiectasia and Rad3-related protein)
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    gemcitabine • camonsertib (RP-3500)
    3ms
    Differential roles of type I topoisomerases in regulating HPV pathogenesis. (PubMed, Proc Natl Acad Sci U S A)
    Finally, TOP1α and TOP3β differentially regulate the formation of R-loops, which are critical for viral replication. These findings demonstrate the differential roles of type I topoisomerases in HPV pathogenesis.
    Journal
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    IL6 (Interleukin 6) • ATR (Ataxia telangiectasia and Rad3-related protein)