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BIOMARKER:

ATM underexpression

i
Other names: ATM, ATA, ATC, ATD, ATDC, TEL1, TELO1, ATM serine/threonine kinase
Entrez ID:
Related biomarkers:
3ms
Inhibition of ATM with KU-55933 Sensitizes Endometrial Cancer Cell Lines to Olaparib. (PubMed, Onco Targets Ther)
Further analysis revealed that KU-55933 potentiates Olaparib-induced cell apoptosis by inhibiting ATM phosphorylation. Our study demonstrates that inhibiting ATM could enhance the sensitivity of endometrial cancer to Olaparib, thereby providing a potential alternative treatment for the clinical treatment of endometrial cancer.
Preclinical • Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A)
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ATM underexpression • BRCA mutation • ATM expression
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Lynparza (olaparib) • KU-55933
7ms
Reduced expression of phosphorylated ataxia-telangiectasia mutated gene is related to poor prognosis and gemcitabine chemoresistance in pancreatic cancer. (PubMed, BMC Cancer)
These findings demonstrate that loss of ATM expression increases tumor development, suppresses apoptosis, and reduces gemcitabine sensitivity. Additionally, loss of phosphorylated ATM is associated with a poor prognosis in patients with pancreatic cancer. Thus, phosphorylated ATM could be a possible target for pancreatic cancer treatment as well as a molecular marker to track patient prognosis.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • NTN1 (Netrin 1)
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MET expression • ATM underexpression • HIF1A expression • ATM expression
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gemcitabine
11ms
ATM Inhibition-Induced ISG15/IFI27/OASL Is Correlated with Immunotherapy Response and Inflamed Immunophenotype. (PubMed, Cells)
The high expressions of ISG15, IFI27, and OASL were also correlated with complete remission in patients with cervical cancer treated with cisplatin. These results suggest that ATM inhibition can induce the interferon response and inflamed TIME, which may benefit ICB therapy.
Journal • Tumor mutational burden • IO biomarker
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TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • IFI27 (Interferon Alpha Inducible Protein 27) • OASL (2'-5'-Oligoadenylate Synthetase Like) • ISG15 (ISG15 Ubiquitin Like Modifier)
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TMB-H • MSI-H/dMMR • ATM underexpression • ATM expression
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cisplatin
over1year
Survival of patients with colorectal cancer (CRC) with low expression of homologous recombination proficient (HRP) genes. (ASCO-GI 2023)
"Background: HR deficient (HRD) CRC has improved outcomes following exposure to DNA damaging agent (DDA) (irinotecan, IR; oxaliplatin, OX) compared to HRP CRC. Here we report the first findings to suggest a novel subclass of CRC defined as the low expression of mRNA of non-mutated HRD genes that exhibit sensitivity to DDA. Low expression of WT ATM, CHEK2, and PALB2 correlates with prolonged OS following IR, post-OX survival was prolonged with low expression of ATM and PALB2. Further characterization defining sensitivity of low expressing HRP genes to DDA may help guide treatment considerations in HRP CRC."
Clinical
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BRCA1 (Breast cancer 1, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2)
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PALB2 mutation • ATM underexpression • BRCA1 expression • ATM expression
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oxaliplatin • irinotecan
over1year
STAT3 and PD-L1 are negatively correlated with ATM and have impact on the prognosis of triple-negative breast cancer patients with low ATM expression. (PubMed, Breast Cancer Res Treat)
Locally advanced TNBC with low ATM expression may be more likely to benefit from anti-PD-L1 inhibitors. The feasibility of ATM functional inhibitor combined with immune checkpoint blockade therapies in the treatment of TNBC is also worthy of further exploration. Our study suggests that STAT3 has different impacts on tumor progression in different tumors.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • STAT3 (Signal Transducer And Activator Of Transcription 3) • STAT1 (Signal Transducer And Activator Of Transcription 1)
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PD-L1 expression • PD-L1 underexpression • PD-L1 negative • ATM underexpression • STAT3 expression • ATM expression
over1year
Interaction between HER2 and ATM predicts poor survival in bladder cancer patients. (PubMed, J Cell Mol Med)
Altogether, our data pinpoint an important biological role of the interconnection between HER2 and ATM. The latter appear to be an independent prognostic biomarker and may serve as targets to develop novel combination therapies to improve the outcome of patients with bladder cancer.
Journal
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 overexpression • HER-2 mutation • ATM underexpression • ATM expression • HER-2-H
almost3years
Downregulation of ATM and BRCA1 Predicts Poor Outcome in Head and Neck Cancer: Implications for ATM-Targeted Therapy. (PubMed, J Pers Med)
The results showed that the expression of ATM and BRCA1 was downregulated in BQ-associated HNC, as the BQ ingredient arecoline could suppress the expression of both genes. Transcriptomic analysis showed that inhibition of ATM kinase by KU55933 induced apoptosis signaling and potentiated cisplatin-induced cytotoxicity. These data unveil poor prognosis in the HNC patient subgroup with low expression of ATM and BRCA1 and support the notion of ATM-targeted therapy.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency)
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ATM underexpression • BRCA1 expression • ATM expression
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cisplatin • KU-55933
almost3years
The Role and Mechanism of ATM-Mediated Autophagy in the Transition From Hyper-Radiosensitivity to Induced Radioresistance in Lung Cancer Under Low-Dose Radiation. (PubMed, Front Cell Dev Biol)
ATM may influence autophagy through p-JNK and AMBRA1 to participate in the regulation of the HRS/IRR phenomenon. Autophagy interacts with the cellular carbon metabolite DL-Norvaline to participate in regulating the low-dose radiosensitivity of cells.
Journal
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BECN1 (Beclin 1) • MAPK8 (Mitogen-activated protein kinase 8)
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ATM underexpression • ATM expression • ATM positive
over3years
Complete loss of ATM function augments replication catastrophe induced by ATR inhibition and gemcitabine in pancreatic cancer models. (PubMed, Br J Cancer)
ATM loss augments replication catastrophe-mediated cell death induced by ATRi/gem and may predict clinical responsiveness to this combination. ATM status should be carefully assessed in tumours from patients with PDAC, since distinction between ATM-low and ATM-null could be critical in maximising the success of clinical trials using ATM expression as a predictive biomarker.
Preclinical • Journal
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CHEK2 (Checkpoint kinase 2) • ATR (Ataxia telangiectasia and Rad3-related protein)
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ATM underexpression • ATM expression
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gemcitabine • ceralasertib (AZD6738)
almost4years
[VIRTUAL] Identification of novel CDK12 inhibitors that synergize with PARP inhibition through induction of ‘BRCAness’ phenotype (AACR-II 2020)
In combination with Olaparib, a clinically approved PARP inhibitor, we observed a synergistic effect on cell viability in the OV-90 ovarian cancer cell line...Overall the compounds demonstrate a phenotype consistent with selective CDK12 inhibition and cellular potency that compares favorably with other published compounds. The compounds have a high potential for being developed as once-daily oral compounds for use in combination with PARP inhibition, immunomodulators and as single agent therapy.
BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • ATR (Ataxia telangiectasia and Rad3-related protein) • CDK1 (Cyclin-dependent kinase 1)
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ATM underexpression • ATM expression
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Lynparza (olaparib)