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    GENE:

    ATM (ATM serine/threonine kinase)

    i
    Other names: ATM, ATA, ATC, ATD, ATDC, TEL1, TELO1, ATM serine/threonine kinase
    5d
    DNA Checkpoint Gene Mutation as a Biomarker for Immune Checkpoint Inhibitor Therapy in Advanced Biliary Tract Cancer. (PubMed, Anticancer Res)
    The DNACHK pathway is expected to serve as a potential biomarker for ICI treatment.
    Journal • Checkpoint inhibition • BRCA Biomarker • IO biomarker • Metastases
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
    |
    ATM mutation
    8d
    Genomic Correlates of Prostate-Specific Membrane Antigen Expression and Response to 177Lu-PSMA-617: A Retrospective Multicenter Cohort Study. (PubMed, JCO Precis Oncol)
    Outcomes on LuPSMA varied on the basis of mutational profile. Prospective studies to define the clinical activity of LuPSMA in predefined genomic subgroups are justified.
    Retrospective data • Journal
    |
    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • RB1 (RB Transcriptional Corepressor 1)
    |
    TP53 mutation • ATM mutation • PTEN mutation • RB1 mutation
    |
    Pluvicto (lutetium Lu 177 vipivotide tetraxetan)
    8d
    Genomic characterization and detection of potential therapeutic targets for peritoneal mesothelioma in current practice. (PubMed, Clin Exp Med)
    Extensive NGS analysis of PeM samples resulted in the identification of potentially effective targeted therapies for about one in four patients. Although these therapies are currently not available for patients with PeM, ongoing developments might result in new treatment options in the future.
    Journal • Tumor mutational burden • BRCA Biomarker
    |
    TMB (Tumor Mutational Burden) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • BAP1 (BRCA1 Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NF2 (Neurofibromin 2)
    |
    BAP1 mutation • NF2 mutation
    |
    FoundationOne® CDx
    8d
    Prognostic impact of genetic abnormalities in 536 first-line chronic lymphocytic leukaemia patients without 17p deletion treated with chemoimmunotherapy in two prospective trials: Focus on IGHV-mutated subgroups (a FILO study). (PubMed, Br J Haematol)
    Our findings highlight the diverse prognostic influence of genetic aberrations depending on the IGHV status in symptomatic CLL patients receiving first-line CIT. The prognosis of gene mutations and cytogenetic abnormalities needs to be investigated with a compartmentalized methodology, taking into account the IGVH status of patients receiving first-line BTK and/or BCL2 inhibitors.
    Journal • IO biomarker
    |
    TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • SF3B1 (Splicing Factor 3b Subunit 1) • IGH (Immunoglobulin Heavy Locus) • SAMHD1 (SAM And HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1)
    |
    TP53 mutation • ATM mutation • Chr del(11q) • IGH mutation • SAMHD1 mutation
    10d
    Randomized Phase II Study of Gemcitabine With or Without ATR Inhibitor Berzosertib in Platinum-Resistant Ovarian Cancer: Final Overall Survival and Biomarker Analyses. (PubMed, JCO Precis Oncol)
    The results of this follow-up analysis continue to support the promise of combined gemcitabine/ATRi therapy in platinum resistant ovarian cancer, an active area of investigation with several ongoing clinical trials.
    P2 data • Journal
    |
    ATM (ATM serine/threonine kinase)
    |
    ATM expression
    |
    gemcitabine • berzosertib (M6620)
    11d
    ATRIUM: A Study of ATG-018 (ATR Inhibitor) Treatment in Patients With Advanced Solid Tumors and Hematological Malignancies (clinicaltrials.gov)
    P1, N=88, Recruiting, Antengene Discovery Limited | Trial primary completion date: Mar 2024 --> Jun 2024
    Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    TP53 mutation • FANCF mutation
    |
    ATG-018
    15d
    Discovery of a Meisoindigo-Derived PROTAC as the ATM Degrader: Revolutionizing Colorectal Cancer Therapy via Synthetic Lethality with ATR Inhibitors. (PubMed, J Med Chem)
    Notably, 9b-induced ATM degradation synergistically enhanced the efficacy of ATR inhibitor AZD6738 both in vitro and in vivo. This work establishes the synthetic lethality-inducing properties of ATR inhibitors in the ATM-deficient context, thereby providing new avenues to innovative therapies for colorectal cancer.
    Journal • Synthetic lethality
    |
    ATM (ATM serine/threonine kinase)
    |
    ceralasertib (AZD6738)
    18d
    Acolbifene Versus Low Dose Tamoxifen for the Prevention of Breast Cancer in Premenopausal Women at High Risk for Development of Breast Cancer (clinicaltrials.gov)
    P2, N=80, Not yet recruiting, National Cancer Institute (NCI) | Phase classification: P2a --> P2 | Initiation date: Mar 2024 --> Oct 2024
    Phase classification • Trial initiation date
    |
    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • NF1 (Neurofibromin 1) • MSH6 (MutS homolog 6) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • AGR2 (Anterior gradient 2)
    |
    TP53 mutation • ATM mutation • PTEN mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • PMS2 mutation • BARD1 mutation • NBN mutation
    |
    tamoxifen • acolbifene
    20d
    Safety of the Breast Cancer Adjuvant Radiotherapy in Ataxia-Telangiectasia Mutated Variant Carriers. (PubMed, Cancers (Basel))
    The same results were observed for late toxicities without an effect from the rs1801516 genotype on toxicities. No significant difference in acute or late toxicities was observed between rare ATM variant carriers and noncarriers after breast RT for localized breast cancer.
    Journal
    |
    ATM (ATM serine/threonine kinase)
    24d
    Identification of a hypoxia-suppressed lncRNA RAMP2-AS1 in breast cancer. (PubMed, Noncoding RNA Res)
    Intriguingly, in vitro experiments confirmed that RAMP2-AS1 was a hypoxia-suppressed lncRNA and miR-660-5p/ATM was a potential downstream axis of RAMP2-AS1 in breast cancer. Collectively, our current data elucidated a key hypoxia-suppressed lncRNA RAMP2-AS1 and its possible miRNA-mRNA regulatory mechanism in breast cancer.
    Journal
    |
    ATM (ATM serine/threonine kinase) • MIR1301 (MicroRNA 1301) • MIR2277 (MicroRNA 2277) • MIR660 (MicroRNA 660)
    1m
    NGS of brush cytology samples improves the detection of high-grade dysplasia and cholangiocarcinoma in patients with primary sclerosing cholangitis: A retrospective and prospective study. (PubMed, Hepatol Commun)
    In summary, NGS of BC samples increased the sensitivity of detecting biliary neoplasia compared with traditional cytology. Performing NGS on BC samples may help diagnose HGD or early CCA, benefiting the timing of liver transplantation.
    Retrospective data • Journal • Next-generation sequencing • Cytology
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • GNAS (GNAS Complex Locus)
    |
    TP53 mutation • BRAF mutation • ATM mutation • RNF43 mutation • GNAS mutation
    1m
    ARIANES: Efficacy and Safety of the Combination of Rucaparib (PARP Inhibitor) and Atezolizumab (Anti-PD-L1 Antibody) in Patients With DNA Repair-deficient or Platinum-sensitive Solid Tumors (clinicaltrials.gov)
    P2, N=130, Suspended, Gustave Roussy, Cancer Campus, Grand Paris | N=1000 --> 130 | Trial primary completion date: Apr 2024 --> Dec 2024
    Enrollment change • Trial primary completion date • Pan tumor
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • IL2 (Interleukin 2) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)
    |
    DDR • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • NBN mutation • DRD
    |
    Tecentriq (atezolizumab) • Rubraca (rucaparib)
    1m
    Promising Response of Olaparib in Patient With Germline ATM-Mutated Metastatic Gastric Cancer. (PubMed, J Investig Med High Impact Case Rep)
    Our case underscores the potential clinical utility of olaparib in germline ATM-mutated gastric cancer and emphasizes the need for further exploration through larger clinical trials. Ongoing research and clinical trials are essential for optimizing the use of PARP inhibitors, identifying biomarkers, and advancing personalized treatment strategies for gastric cancer.
    Journal • PARP Biomarker • IO biomarker • Metastases
    |
    ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency)
    |
    ATM mutation
    |
    Lynparza (olaparib)
    1m
    TRITON3: A Study of Rucaparib Versus Physician's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency (clinicaltrials.gov)
    P3, N=405, Active, not recruiting, pharmaand GmbH | Trial completion date: Mar 2024 --> Dec 2024
    Trial completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • BRCA1 mutation + ATM mutation
    |
    docetaxel • Xtandi (enzalutamide capsule) • Rubraca (rucaparib) • abiraterone acetate
    1m
    Evaluation of Ataxia-Telangiectasia Mutated IVS10 Mutation in Breast Cancer Along with Clinicopathological Parameters. (PubMed, J Midlife Health)
    Majority of cases were luminal B (11; 30.56%) followed by triple negative (10; 27.78%). Although the results obtained by mutational analysis in the present study are not in agreement with the previous study on Indian women it agrees with the numerous previous studies and meta-analyses done on women with breast carcinoma in the Western world.
    Journal • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2)
    2ms
    PancreasScan: Pancreatic Cancer Screening for At-risk Individuals (clinicaltrials.gov)
    P=N/A, N=500, Recruiting, Beth Israel Deaconess Medical Center | Trial completion date: Jul 2026 --> Mar 2028 | Trial primary completion date: Jul 2025 --> Mar 2027
    Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • EPCAM (Epithelial cell adhesion molecule) • PRSS1 (Serine Protease 1)
    |
    BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CDKN2A mutation • MLH1 mutation • PMS2 mutation • BRCA mutation
    2ms
    Targeting ATR Pathway in Solid Tumors: Evidence of Improving Therapeutic Outcomes. (PubMed, Int J Mol Sci)
    In addition, ATR inhibition plays a significant role in the activation of the immune system by increasing the tumor mutational burden and neoantigen load as well as by triggering the accumulation of cytosolic DNA and subsequently inducing the cGAS-STING pathway and the type I IFN response. Taken together, we review stimulating data showing that ATR kinase inhibition can alter the DDR network, the immune system, and their interplay and, therefore, potentially provide a novel strategy to improve the efficacy of antitumor therapy, using ATR inhibitors as monotherapy or in combination with genotoxic drugs and/or immunomodulators.
    Review • Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • ATM (ATM serine/threonine kinase)
    |
    ceralasertib (AZD6738)
    2ms
    Retrospective genetic testing (Traceback) in women with early-onset breast cancer after revised national guidelines: a clinical implementation study. (PubMed, Breast Cancer Res Treat)
    The insights from the participants' perspectives and sentiments throughout the process support the notion that the Traceback procedure is a safe and an appreciated complement to routine genetic counseling. The genetic yield of almost 10% also suggests that the associated extra workload for genetic counselors could be viewed as acceptable in clinical implementation scenarios.
    Retrospective data • Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
    2ms
    Computational Analysis of Non-synonymous SNPs in ATM Kinase: Structural Insights, Functional Implications, and Inhibitor Discovery. (PubMed, Mol Biotechnol)
    Molecular docking and dynamic simulation analyses highlight strong binding affinities of quercetin for Y2080D and AZD0156 for C2770G, suggesting potential therapeutic options...The study underscores the significance of Y2080D and C2770G mutations, offering valuable insights for future precision medicine targeting-specific ATM. Despite informative computational analyses, a significant research gap exists, necessitating essential in vitro and in vivo studies to validate the predicted effects of ATM mutations on protein structure and function.
    Journal
    |
    ATM (ATM serine/threonine kinase)
    |
    AZD1390 • AZD0156
    2ms
    A Study of Pembrolizumab and Olaparib for People With Metastatic Pancreatic Ductal Adenocarcinoma and Homologous Recombination Deficiency or Exceptional Treatment Response to Platinum-Based Therapy (clinicaltrials.gov)
    P2; Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • BAP1 (BRCA1 Associated Protein 1) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FANCC (FA Complementation Group C)
    |
    MSK-IMPACT
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib)
    2ms
    Variant ataxia telangiectasia identified during evaluation for short stature. (PubMed, BMJ Case Rep)
    Since diagnosis, she has developed progressive cerebellar ataxia and telangiectasias. Long-standing restrictive and aversive feeding behaviours presented challenges for her management and necessitated gastrostomy.
    Journal
    |
    ATM (ATM serine/threonine kinase)
    |
    ATM mutation
    2ms
    TP53 mutation is frequent in mantle cell lymphoma with EZH2 expression and have dismal outcome when both are present. (PubMed, Hum Pathol)
    p53 mutant pattern is due to TP53 mutation. MCL patients with EZH2 expression or TP53 mutation show inferior outcome and when both are present, patients have dismal outcome.
    Journal
    |
    TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
    |
    TP53 mutation • EZH2 mutation • TP53 expression
    2ms
    A Phase II Study of Rucaparib Monotherapy in Nonmetastatic, Hormone-Sensitive Prostate Cancer Demonstrating "BRCAness" Genotype (ROAR). (PubMed, Oncologist)
    Rucaparib demonstrated acceptable toxicity and efficacy signal as an ADT-sparing approach in patients with biochemically recurrent nonmetastatic prostate cancer. It is currently challenging to understand the optimal value of systemic therapy in this disease setting due to the rapidly changing standard of care. Additionally, there are relatively few patients with BRCAness who present with nonmetastatic hormone-sensitive prostate cancer (ClinicalTrials.gov Identifier: NCT03533946).
    P2 data • Journal • BRCA Biomarker • PARP Biomarker • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
    |
    ATM mutation • PALB2 mutation • CHEK2 mutation • RAD51 mutation
    |
    Rubraca (rucaparib)
    2ms
    Germline variants of DNA repair and immune genes in lymphoma from lymphoma-cancer families. (PubMed, Int J Cancer)
    In DLBCLs with germline PTVs of ATM, deletion and insertion in CD58 were further revealed. Thus, in lymphoma-cancer families, we identified germline defects of both DNA repair and immune genes in lymphoma patients.
    Journal
    |
    ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • BCL6 (B-cell CLL/lymphoma 6) • CD58 (CD58 Molecule)
    |
    HRD • ATM deletion
    2ms
    Comprehensive germline profiling of patients with breast cancer: initial experience from a Familial Cancer Clinic. (PubMed, Ecancermedicalscience)
    Age and triple-negative histology were not found to be significantly associated with the occurrence of P/LP PVs. We report a 41% P/LP variant rate in our selected cohort of breast cancer patients, with variants in BRCA constituting 83% and non-BRCA gene variants constituting 17%.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A)
    2ms
    Safety and Efficacy of AMT-RegeneraActiva in the Management of Knee Osteoarthritis (OA) (clinicaltrials.gov)
    P=N/A, N=60, Not yet recruiting, Human Brain Wave S.r.l. | Initiation date: Nov 2023 --> Mar 2024
    Trial initiation date
    |
    ATM (ATM serine/threonine kinase)
    2ms
    Treatment patterns and outcomes in metastatic castration-resistant prostate cancer patients with and without somatic or germline alterations in homologous recombination repair genes. (PubMed, Ann Oncol)
    Worse outcomes were observed for mCRPC patients in the BRCA subgroup compared with non-BRCA subgroups, either HRR non-BRCA or non-HRR. Despite its heterogeneity, the HRR non-BRCA subgroup presented worse outcomes than the non-HRR subgroup. Screening early for HRR mutations, especially BRCA1/2, is crucial in improving mCRPC patient prognosis.
    Journal • BRCA Biomarker • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • HDAC2 (Histone deacetylase 2)
    |
    BRCA2 mutation • BRCA1 mutation
    2ms
    Ataxia-Telangiectasia Mutated (ATM) loss of function displays variant and tissue-specific differences across tumor types. (PubMed, Clin Cancer Res)
    These data help to better define ATM LOF across tumor types in order to optimize patient selection and improve molecularly targeted therapeutic approaches for patients with ATM LOF cancers.
    Journal
    |
    ATM (ATM serine/threonine kinase)
    |
    ATM mutation
    |
    ART0380
    2ms
    Prospective Screening for Pancreatic Ductal Adenocarcinoma in High-Risk Individuals (clinicaltrials.gov)
    P1, N=5000, Recruiting, Dana-Farber Cancer Institute | Not yet recruiting --> Recruiting | Initiation date: Nov 2024 --> Nov 2023
    Enrollment open • Trial initiation date
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • EPCAM (Epithelial cell adhesion molecule) • PRSS1 (Serine Protease 1)
    2ms
    Genomic landscape of liquid biopsy mutations in TP53 and DNA damage genes in cancer patients. (PubMed, NPJ Precis Oncol)
    P1; In a subset of 37 patients, 75.0%, 53.5% and 83.3% of the liquid biopsy-only mutations occurring respectively in ATM, TP53, and CHEK2 were confirmed in the matching whole blood sample. Although liquid biopsy-only mutations makes the interpretation of liquid biopsy results more complex, they have distinct characteristics making them more easily identifiable.
    Journal • BRCA Biomarker • Liquid biopsy • Biopsy
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2) • STING (stimulator of interferon response cGAMP interactor 1)
    |
    TP53 mutation • ATM mutation • CHEK2 mutation
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    2ms
    A Study of Reduced-dose Radiation in People With Metastatic Tumors With a Genetic Change (clinicaltrials.gov)
    P2, N=29, Recruiting, Memorial Sloan Kettering Cancer Center | N=58 --> 29
    Enrollment change
    |
    ATM (ATM serine/threonine kinase)
    |
    ATM mutation
    2ms
    A-T neurodegeneration and DNA damage-induced transcriptional stress. (PubMed, DNA Repair (Amst))
    In addition, innate immunity signaling pathways appear to play a critical role in ATM functions in microglia, responding to various forms of nucleic acid sensors and regulating survival of neurons and other cell types. Overall, the results lead to an updated view of transcriptional stress and DNA damage resulting from ATM loss that results in changes in gene expression as well as neuroinflammation that contribute to the cerebellar neurodegeneration observed in patients.
    Journal
    |
    ATM (ATM serine/threonine kinase)
    |
    ATM expression
    3ms
    Niraparib in Patients With Pancreatic Cancer (clinicaltrials.gov)
    P2, N=32, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Sep 2023 --> Sep 2024
    Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation
    |
    Zejula (niraparib)
    3ms
    Pancreas Registry and High Risk Registry (clinicaltrials.gov)
    P=N/A, N=1116, Recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: Dec 2023 --> Nov 2033 | Trial primary completion date: Dec 2023 --> Nov 2033
    Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MSH2 (MutS Homolog 2)
    |
    ATM mutation • STK11 mutation • PALB2 mutation • CDKN2A mutation
    3ms
    A Study of ART0380 for the Treatment of Advanced or Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=372, Recruiting, Artios Pharma Ltd | N=242 --> 372
    Enrollment change • Metastases
    |
    ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    HRD • BRCA mutation
    |
    gemcitabine • irinotecan • ART0380
    3ms
    Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma. (PubMed, Cell Death Dis)
    Despite that the docectaxel-cisplatin-5-fluorouracil (TPF) induction chemotherapy has greatly improved patients' survival and became the first-line treatment for advanced nasopharyngeal carcinoma (NPC), not all patients could benefit from this therapy. We further confirm that ATMIN transcriptionally activates the downstream target gene LCK and stabilizes it to facilitate cell proliferation and docetaxel resistance. Taken together, our findings broaden the insight into the molecular mechanism of chemoresistance in NPC, and the USP10-ATMIN-LCK axis provides potential therapeutic targets for the management of NPC.
    Journal
    |
    ATM (ATM serine/threonine kinase) • LCK (LCK Proto-Oncogene, Src Family Tyrosine Kinase)
    |
    cisplatin • docetaxel • 5-fluorouracil
    3ms
    Gender-Specific Genetic Predisposition to Breast Cancer: BRCA Genes and Beyond. (PubMed, Cancers (Basel))
    Evaluating the genetic component of male BC as a distinct entity from female BC is the first step to improve both personalized risk assessment and therapeutic choices of patients of both sexes in order to reach gender equality in BC care. In this review, we summarize the latest research in the field of BC genetic predisposition with a particular focus on similarities and differences in male and female BC, and we also discuss the implications, challenges, and open issues that surround the establishment of a gender-oriented clinical management for BC.
    Review • Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2)
    3ms
    TRIUMPH: Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (clinicaltrials.gov)
    P2, N=30, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting
    Enrollment closed
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C)
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    CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • FANCF mutation • NBN mutation • FANCG mutation • FANCI mutation • FANCM mutation
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    Rubraca (rucaparib)
    3ms
    Identification of Two Novel Pathogenic Variants of the ATM Gene in the Iranian-Azeri Turkish Ethnic Group by Applying Whole Exome Sequencing. (PubMed, Curr Genomics)
    Genetic analysis of three unrelated families with ATM-related disorders discovered two novel pathogenic variants. A homozygous missense pathogenic variant was identified in a woman with bi-lateral breast cancer, and a synonymous but pathogenic variant was found in a family with a history of different cancers.
    Journal
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    ATM (ATM serine/threonine kinase)
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    ATM mutation
    3ms
    Discovery of the first ataxia telangiectasia and Rad3-related (ATR) degraders for cancer treatment. (PubMed, Eur J Med Chem)
    Proteasome-mediated ATR degradation by ZS-7 lasted approximately 12 h after washout in the LoVo cell lines. Notably, ZS-7 demonstrated reasonable PK profiles and, as a single agent or in combination with cisplatin, showed improved antitumor activity and safety profiles compared with the parent inhibitor AZD6738 in a xenograft mouse model of LoVo human colorectal cancer cells upon intraperitoneal (i.p.) administration.
    Journal
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    ATM (ATM serine/threonine kinase) • ATR (Ataxia telangiectasia and Rad3-related protein)
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    cisplatin • ceralasertib (AZD6738)
    3ms
    Uncovering the clinical relevance of unclassified variants in DNA repair genes: a focus on BRCA negative Tunisian cancer families. (PubMed, Front Genet)
    Our findings revealed that VUSs in DNA repair genes might be associated with increased cancer risk and highlight the need for variant reclassification for better disease management. This will help to improve the genetic diagnosis and therapeutic strategies of cancer patients not only in Tunisia but also in neighboring countries.
    Journal
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    ATM (ATM serine/threonine kinase) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit) • FANCG (FA Complementation Group G) • FANCC (FA Complementation Group C)
    3ms
    TRIP13 Enhances Radioresistance of Lung Adenocarcinoma Cells through the Homologous Recombination Pathway (PubMed, Zhongguo Fei Ai Za Zhi)
    TRIP13 is associated with poor prognosis in LUAD patients treated with radiation, possibly by promoting a homologous recombination repair pathway to mediate resistance of LUAD cells to radiation.
    Journal
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    ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • TRIP13 (Thyroid Hormone Receptor Interactor 13)