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GENE:

ATM (ATM serine/threonine kinase)

News alerts, weekly reports and conference planners

Pathogenic variants in cancer susceptibility genes predispose to Ductal Carcinoma In situ of the breast. (PubMed, Clin Cancer Res)

The enrichment of PVs in ATM, BRCA1, BRCA2, CHEK2 and PALB2 among women with DCIS suggests that multigene panel testing may be appropriate for women with DCIS. Elevated risks of contralateral breast cancer in carriers of PVs in high penetrance genes with DCIS confirmed the utility of testing for surgical decision-making.

3 days ago

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) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)

Germline sequencing in men with metastatic castration-resistant prostate cancer from the BARCODE2 study reveals a wide range of pathogenic variants in DNA repair genes. (PubMed, BJC Rep)

Germline pathogenic/likely pathogenic (P/LP) variants in BRCA2 and ATM genes are associated with a shorter time to progression and rarer P/LP variants in other DRG genes may play a role in mCRPC. This justifies the use of routine screening of men with advanced PrCa for germline variants and supports the need for an expanded panel test.

3 days ago

Journal • BRCA Biomarker • Metastases

BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase)

carboplatin

Splicing Dysregulation of Non-Canonical GC-5' Splice Sites of Breast Cancer Susceptibility Genes ATM and PALB2. (PubMed, Cancers (Basel))

The mapping of SRE-rich intervals in minigenes is a valuable approach for the identification of spliceogenic variants that outperforms any prediction software. Indeed, 12 spliceogenic SRE-variants were identified in the critical intervals.

3 days ago

Journal

ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • SRSF2 (Serine and arginine rich splicing factor 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)

Radiation Therapy (RT) and Chemotherapy for the Treatment of Pancreatic Cancer with Homologous Recombination Deficiency That Has Spread to the Liver (clinicaltrials.gov)

P1, N=1, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Nov 2024 | Trial primary completion date: Dec 2025 --> Nov 2024

6 days ago

Trial completion • Trial completion date • Trial primary completion date

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)

BRCA1 mutation • PALB2 mutation

MSK-IMPACT

cisplatin • gemcitabine

11d

PancreasScan: Pancreatic Cancer Screening for At-risk Individuals (clinicaltrials.gov)

P=N/A, N=1395, Recruiting, Beth Israel Deaconess Medical Center | N=500 --> 1395 | Trial completion date: Mar 2028 --> Dec 2032 | Trial primary completion date: Mar 2027 --> Dec 2032

11 days ago

Enrollment change • 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

12d

Computer-aided Drug Discovery of Epigenetic Modulators in Dual-target Therapy of Multifactorial Diseases. (PubMed, Curr Top Med Chem)

The detailed anticancer mechanisms by which the epigenetic dual-target inhibitors alter metastatic and tumorigenic properties, influence the tumor microenvironment, or regulate the immune response are also presented and discussed in the review. To improve our understanding of the pathogenesis of cancer and neurodegeneration, this review discusses novel therapeutic agents targeting different molecular mechanisms involved in these multifactorial diseases.

12 days ago

Journal

ATM (ATM serine/threonine kinase) • BDNF (Brain Derived Neurotrophic Factor)

13d

Random Threshold Model: A Low-Dose Radiation-Induced Risk Assessment Approach Considering Individual Susceptibility to Cancer. (PubMed, Dose Response)

For cancer risk associated with low-dose radiation exposure, the contribution of radiosensitivity cannot be ignored, thus the RT model would be more suitable for risk protection for radiosensitive subgroups instead of the LNT model. We also notice that it could be widely applicable for risk protection of not only low-dose radiation but also environmental pollutants.

13 days ago

Journal

ATM (ATM serine/threonine kinase)

13d

Radiation Therapy (RT) and Chemotherapy for the Treatment of Pancreatic Cancer With Homologous Recombination Deficiency That Has Spread to the Liver (clinicaltrials.gov)

P1, N=1, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

13 days ago

Trial completion date • Trial primary completion date • Metastases

BRCA1 mutation • PALB2 mutation

MSK-IMPACT

cisplatin • gemcitabine

18d

Tissue microarray analyses of the essential DNA repair factors ATM, DNA-PKcs and Ku80 in head and neck squamous cell carcinoma. (PubMed, Radiat Oncol)

Our data suggest that HPV-negative HNSCC with particularly low Ku80 expression represent a highly radiosensitive subpopulation. Confirmation in independent cohorts is required.

18 days ago

Journal

ATM (ATM serine/threonine kinase)

ATM expression

18d

Association of ATM and ARID1A in gastric carcinoma. (PubMed, Pathol Res Pract)

ATMlow in GCs shows a characteristic clinicopathological feature that correlates strongly with ARID1Alow. ATM mutation was also associated with ARID1A mutations, highlighting the interactions between ATM and ARID1A in GC and suggesting a potential therapeutic target.

18 days ago

Journal • MSi-H Biomarker

MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A)

MSI-H/dMMR • ARID1A mutation • ATM underexpression • ATM expression

19d

A Complete Response to Combined Immunotherapy in a Patient with an ATM plus SF3B1 Mutation and a Moderate Tumor Mutational Burden with a High-Grade Treatment-Emergent Neuroendocrine Prostate Cancer: Case Report and Review of the Literature. (PubMed, Case Rep Oncol)

We describe an impressive response to IO combination immunotherapy with ipilimumab plus nivolumab (Ipi/nivo) in a patient with T-NEPC who had failed standard treatment approaches. The results of the next-generation sequencing DNA analysis demonstrated the presence of intermediary tumor burden, an ATM mutation and a rare SF3B1 (G742D) mutation, and served as rational for IO therapy in this patient. This case highlights the genetic profile of tumor with a rare combination of ATM and SF3B1 mutations that could be further explored as biomarkers for IO therapy in T-NEPC and other tumor types.

19 days ago

Review • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker

TMB (Tumor Mutational Burden) • ATM (ATM serine/threonine kinase) • SF3B1 (Splicing Factor 3b Subunit 1)

ATM mutation • SF3B1 mutation

Opdivo (nivolumab) • Yervoy (ipilimumab)

24d

A Translational Study of the ATR Inhibitor Berzosertib as Monotherapy in Four Molecularly Defined Cohorts of Advanced Solid Tumors. (PubMed, Clin Cancer Res)

Across cohorts, only SDH-mutant GIST patients experienced prolonged disease control. Despite evidence of target engagement, patients enrolled to all other cohorts had short PFS, suggesting rapid adaptation to ATR inhibitor monotherapy. Among these patients, those with tumors expressing SLFN11 during berzosertib exposure derived the most clinical benefit.

24 days ago

Journal • Metastases

ATM (ATM serine/threonine kinase) • SLFN11 (Schlafen Family Member 11) • ATRX (ATRX Chromatin Remodeler) • CHEK1 (Checkpoint kinase 1)

ATM mutation • ATRX mutation

berzosertib (M6620)

26d

Osteosarcoma patient with Li-Fraumeni syndrome: the first case report in Vietnam. (PubMed, Front Oncol)

This case highlights the importance of genetic testing for the early detection and management of cancers in LFS patients. It also underscores significant barriers to genetic screening in Vietnam, including limited access and the psychosocial consequences of testing, which emphasize the need for improved genetic counseling and surveillance strategies that are tailored to local contexts.

26 days ago

Journal

TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase)

TP53 mutation

27d

Strong association of single nucleotide polymorphisms in BRCA1, ATM, and CHEK2 with breast cancer susceptibility in a sub-population of Iranian women. (PubMed, Breast Cancer Res Treat)

Our results indicated that BRCA1, ATM, and CHEK2 polymorphisms have a high frequency in the Iranian breast cancer population, with some mutant allele frequencies being much higher than those reported in other populations. We have also provided a simple, multiplex, rapid, and accurate genotyping assay that is useful in clinical settings.

27 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2)

27d

Niraparib in Patients With Pancreatic Cancer (clinicaltrials.gov)

P2, N=32, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

27 days ago

Trial completion date • 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)

TRIUMPH: Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (clinicaltrials.gov)

P2, N=12, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed | N=30 --> 12

1 month ago

Trial completion • Enrollment change • Metastases

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)

CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • FANCF mutation • NBN mutation • FANCG mutation • FANCI mutation • FANCM mutation

Rubraca (rucaparib)

SPORE: 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, N=63, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

1 month ago

Enrollment closed • Metastases

MSK-IMPACT

Keytruda (pembrolizumab) • Lynparza (olaparib)

Double Hit in Clear-Cell Renal Cell Carcinoma With Germline Pathogenic ATM Mutation and Somatic VHL Mutation. (PubMed, J Investig Med High Impact Case Rep)

This case highlights the potential use for enhanced screening protocols for RCC in patients who have germline pathogenic ATM mutations and the importance of research in targeted treatments for tumors driven by dual genetic mechanisms. Increased awareness and vigilant screening for RCC are crucial in managing hereditary cancer syndromes effectively.

1 month ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • VHL (von Hippel-Lindau tumor suppressor) • BRCA (Breast cancer early onset)

TP53 mutation • ATM mutation • VHL mutation • BRCA mutation

2ms

CHARACTERIZATION OF GENETIC ANCESTRY IN WOMEN DIAGNOSED WITH TRIPLE NEGATIVE BREAST AND HIGH-GRADE SEROSOUS OVARIAN CANCER, HEREDITARY/SPORADIC: IMPLEMENTATION OF A DIAGNOSTIC PANEL (IGCS 2024)

116 patients with a confirmatory primary diagnosis of TNBC (N= 75) and HGSOC (N= 41) were included. A higher Native American ancestry (NAM) proportion was observed in the hereditary group across the cohort (58% vs 45.2%). Among TNBC patients, hereditary cases exhibited a higher NAM ancestry mean (0.50 (SD, 0.14)).

2 months ago

Clinical • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PMS2 mutation • CDH1 mutation

TruSight Hereditary Cancer Panel

2ms

D5330C00004: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents (clinicaltrials.gov)

P1/2, N=466, Recruiting, AstraZeneca | Trial completion date: Jul 2026 --> Mar 2025 | Trial primary completion date: Jul 2026 --> Mar 2025

2 months ago

Trial completion date • Trial primary completion date

HER-2 (Human epidermal growth factor receptor 2) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

HER-2 negative • HRD • PALB2 mutation • RAD51C mutation • BRCA mutation • RAD51 mutation

Lynparza (olaparib) • carboplatin • Imfinzi (durvalumab) • ceralasertib (AZD6738) • saruparib (AZD5305)

2ms

Homologous recombination deficiency gene panel analysis results in synchronous endometrial and ovarian cancers. (PubMed, Rev Assoc Med Bras (1992))

Pathogenic variations confirming the diagnosis of synchronous endometrial ovarian cancer with genetic alterations were identified in all but one case. ATM gene mutation emerged as the most common alteration and has a potential association with a favorable prognosis.

2 months ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • 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) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54)

TP53 mutation • HRD • RAD51D mutation • BARD1 mutation • RAD54L mutation • TP53 mutation + ATM mutation

2ms

Synchronous Pancreatic Ductal Adenocarcinoma and Nasopharyngeal Carcinoma With Associated Novel Pathogenic ATM Mutation. (PubMed, Anticancer Res)

To the best of our knowledge, this is the first documented case of synchronous PDAC and NPC in a patient with novel associated pathogenic ATM c.8545C>T (p.Arg2849*) mutation and poor prognosis. More similar case reports are needed to further characterize this entity.

2 months ago

Journal

ATM (ATM serine/threonine kinase)

ATM mutation

gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • oxaliplatin • irinotecan • leucovorin calcium

2ms

What About the Others? Clinical Management of Gynecologic Cancer Risk in Patients With Moderate-Risk Hereditary Cancer Genes (ATM, BRIP1, RAD51C, RAD51D, and PALB2). (PubMed, Clin Obstet Gynecol)

The associated cancer risks with moderate-penetrance genes are rapidly evolving and present variable risks for the provider counseling the patient. In this review, we detail the cancer risk and management of patients with germline PV in the moderate-risk hereditary cancer genes ATM, BRIP1, RAD51C, RAD51D, and PALB2.

2 months ago

Journal

ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

2ms

Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline ATM sequence variants. (PubMed, Am J Hum Genet)

Overall, 28 of the 33 pilot variants were not VUS, leading to an 85% classification rate. The ClinGen-approved, modified rules demonstrated value for improved interpretation of variants in ATM.

2 months ago

Journal

ATM (ATM serine/threonine kinase)

2ms

Germline genetic variants that predispose to myeloproliferative neoplasms and hereditary myeloproliferative phenotypes. (PubMed, Leuk Res)

Knowledge of those genes and germline genetic changes which lead to MPN or diseases that mimic MPN helps to improve accuracy of diagnosis, aids with counselling regarding familial risk, and may contribute to clinical decision-making. Large scale population exome and genome sequencing studies will improve our knowledge of both common and rare germline genetic contributions to MPN.

2 months ago

Review • Journal

ATM (ATM serine/threonine kinase) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • MECOM (MDS1 And EVI1 Complex Locus) • DDX41 (DEAD-Box Helicase 41) • SH2B3 (SH2B Adaptor Protein 3)

2ms

Prediction of radiotherapy toxicity: 20 years of COPERNIC radiosensitivity diagnosis procedure. (PubMed, Cancer Radiother)

The maximal number of pATM foci appears to be one of the most reliable biomarkers for predicting post-radiotherapy radiotoxicity.

2 months ago

Journal

ATM (ATM serine/threonine kinase)

2ms

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, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial primary completion date: Sep 2026 --> Aug 2027

2 months ago

Enrollment open • Trial primary completion 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

2ms

Comprehensive genetic analysis by targeted sequencing identifies risk factors and predicts patient outcome in Mantle Cell Lymphoma: results from the EU-MCL network trials. (PubMed, Leukemia)

Genetic complexity (≥3 CNVs) observed in 51% of analysed patients was significantly associated with impaired FFS and OS. We demonstrate that targeted sequencing from peripheral blood and bone marrow reliably detects diagnostically and prognostically important genetic factors in MCL patients, facilitating genetic characterization in clinical routine.

2 months ago

Journal

TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • KMT2D (Lysine Methyltransferase 2D) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • BIRC3 (Baculoviral IAP repeat containing 3) • NFKBIE (NFKB Inhibitor Epsilon)

TP53 mutation • ATM mutation • CDKN2A deletion

2ms

ATM phosphorylation of CD98HC increases antiporter membrane localization and prevents chronic toxic glutamate accumulation in Ataxia telangiectasia. (PubMed, Res Sq)

Bypassing the antiporters restores intracellular metabolic balance both in ATM-deficient cells and mouse models. These findings provide new insight into the long-known benefits of N-acetyl cysteine to A-T cells beyond oxidative stress through removing excess glutamate by production of glutathione.

2 months ago

Journal

ATM (ATM serine/threonine kinase) • SLC3A2 (Solute Carrier Family 3 Member 2) • SLC7A5 (Solute Carrier Family 7 Member 5)

2ms

Tannic acid elicits differential gene regulation in prostate cancer apoptosis. (PubMed, Acta Pharm)

These findings highlight tannic acid's ability to induce apoptosis in prostate cancer cells through pro-apoptotic pathways. This study concludes that tannic acid selectively inhibits prostate cancer cell growth.

2 months ago

Journal • IO biomarker

TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • ATM (ATM serine/threonine kinase) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • TNFRSF8 (TNF Receptor Superfamily Member 8) • TNFRSF17 (TNF Receptor Superfamily Member 17) • CHEK2 (Checkpoint kinase 2) • BIRC3 (Baculoviral IAP repeat containing 3) • CD70 (CD70 Molecule) • FASLG (Fas ligand) • BIRC2 (Baculoviral IAP Repeat Containing 2) • CASP3 (Caspase 3) • BCL2A1 (BCL2 Related Protein A1) • CASP8 (Caspase 8) • TNFSF13B (TNF Superfamily Member 13b) • CASP6 (Caspase 6, apoptosis-related cysteine peptidase) • CD40 (CD40 Molecule) • TNFRSF10D (TNF Receptor Superfamily Member 10d) • TNFSF4 (TNF Superfamily Member 4) • TRAF1 (TNF Receptor Associated Factor 1) • PPIA (Peptidylprolyl Isomerase A) • RPA3 (Replication Protein A3)

2ms

Rapid Remission With Upadacitinib in a Child With Refractory Crohn's Disease and ATM Mutation: A Case Report. (PubMed, Curr Ther Res Clin Exp)

This case report delineates successful remission with upadacitinib in a child with CD refractory to infliximab, ustekinumab, adalimumab, thalidomide, and prednisone. Notably, the patient carried an ataxia telangiectasia mutated (ATM) gene mutation. These findings provide valuable evidence for PCD management and highlight the potential benefits of upadacitinib in this population.

2 months ago

Journal

ATM (ATM serine/threonine kinase) • TNFA (Tumor Necrosis Factor-Alpha)

ATM mutation

prednisone • thalidomide

2ms

Prevalence of germline variants in Brazilian pancreatic carcinoma patients. (PubMed, Sci Rep)

Therefore, genetic testing should be offered to all Brazilian pancreatic cancer patients, regardless of their ancestry. Genes with limited or previously unrecognized associations with pancreatic cancer should be further investigated to clarify their role in cancer risk.

2 months ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PALB2 (Partner and localizer of BRCA2) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • MRE11A (MRE11 homolog, double strand break repair nuclease) • MUTYH (MutY homolog) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCM (FA Complementation Group M) • FANCE (FA Complementation Group E) • MITF (Melanocyte Inducing Transcription Factor) • RECQL4( RecQ Like Helicase 4) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

3ms

Clinical utility of BRCA and ATM mutation status in circulating tumour DNA for treatment selection in advanced pancreatic cancer. (PubMed, Br J Cancer)

Comprehensive ctDNA profiling provides clinically relevant information regarding HRD status. It can be a practical, convenient option for HRD screening in APC.

3 months ago

Journal • BRCA Biomarker • Circulating tumor DNA • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)

Guardant360® CDx

gemcitabine • albumin-bound paclitaxel

3ms

D5330C00004: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents (clinicaltrials.gov)

P1/2, N=466, Recruiting, AstraZeneca | Trial completion date: Dec 2026 --> Jul 2026 | Trial primary completion date: Dec 2026 --> Jul 2026

3 months ago

Trial completion date • Trial primary completion date • Combination therapy • Metastases

Lynparza (olaparib) • carboplatin • Imfinzi (durvalumab) • ceralasertib (AZD6738) • saruparib (AZD5305)

3ms

Preliminary Evaluation of Screening for Pancreatic Cancer in Patients With Inherited Genetic Risk (clinicaltrials.gov)

P=N/A, N=200, Recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: May 2027 --> May 2028 | Trial primary completion date: May 2025 --> May 2026

3 months ago

Trial completion date • Trial primary completion date

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2)

3ms

Real-world data on the prevalence of BRCA1/2 and HRR gene mutations in patients with primary and metastatic castration resistant prostate cancer. (PubMed, World J Urol)

This study offers valuable real-world insights into the landscape of BRCA1/2 and HRR gene mutations and the practical clinical management of HRR gene testing in prostate cancer, contributing to a better understanding of patient eligibility for PARPi treatment.

3 months ago

Journal • Real-world evidence • BRCA Biomarker • PARP Biomarker • Real-world • 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) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • HDAC2 (Histone deacetylase 2)

Lynparza (olaparib)

3ms

Comparative analysis of the mutational landscape and evolutionary patterns of pancreatic ductal adenocarcinoma metastases in the liver or peritoneum. (PubMed, Heliyon)

PDAC peritoneal and liver metastases may differ in potential therapeutic biomarkers. Further inquiry is needed on the biological mechanisms underlying metastasis and the treatment of diverse metastases.

3 months ago

Journal • Tumor mutational burden • BRCA Biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • ATM (ATM serine/threonine kinase)

3ms

Testing the Combination of Two Anti-cancer Drugs, Peposertib (M3814) and M1774 for Advanced Solid Tumors (clinicaltrials.gov)

P1, N=66, Recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2024 --> Aug 2026 | Trial primary completion date: Aug 2024 --> Aug 2026

3 months ago

Trial completion date • Trial primary completion date • Combination therapy • Metastases

ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • PBRM1 (Polybromo 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • ARID1B (AT-Rich Interaction Domain 1B) • ARID2 (AT-Rich Interaction Domain 2) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex)

peposertib (M3814) • tuvusertib (M1774)

3ms

Case report: ATM A1159T mutation in malignant peritoneal mesothelioma may be associated with tumor recurrence. (PubMed, SAGE Open Med Case Rep)

In terms of genetic screening, BAP1, CSF1R, and other key driver gene variants closely related to malignant peritoneal mesothelioma have been explored in tumor tissues. Notably, CARD11 driver mutation was first found in all malignant peritoneal mesothelioma patients, and ATM A1159T gene mutation found in recurrent focal tissue may be associated with recurrent tumor recurrence.

3 months ago

Journal

ATM (ATM serine/threonine kinase) • BAP1 (BRCA1 Associated Protein 1) • WT1 (WT1 Transcription Factor) • CARD11 (Caspase Recruitment Domain Family Member 11) • CSF1R (Colony stimulating factor 1 receptor)

3ms

Use of Radiation Therapy for Ataxia-Telangiectasia Mutated (ATM)-Mutation Metastatic Renal Cell Carcinoma: A Case Report. (PubMed, Cureus)

After progression of disease (POD) on ipilimumab/nivolumab, followed by POD on cabozantinib, the patient was treated with radiation therapy to metastatic cervical lymphadenopathy to 60 Gy in 15 fractions as well as retroperitoneal lymphadenopathy to 36 Gy in 9 fractions, which was curtailed due to intolerance. This was followed by sequential systemic therapy with a poly (ADP-ribose) polymerase (PARP) inhibitor and pembrolizumab, which was also discontinued due to adverse effects. Despite not receiving any treatment for 10 months, his disease remains stable. We believe that the prolonged progression-free survival of this patient with ATM-mutation metastatic pRCC is likely due to the enhanced sensitivity of the tumor to radiation therapy due to ATM loss.

3 months ago

Journal • PARP Biomarker • PD(L)-1 Biomarker • Metastases

ATM (ATM serine/threonine kinase)

Keytruda (pembrolizumab) • Opdivo (nivolumab) • Yervoy (ipilimumab) • Cabometyx (cabozantinib tablet)

3ms

Ataxia telangiectasia-mutated rs56009889 and risk of common cancers. (PubMed, Eur J Cancer Prev)

Among the breast cancer subjects, the OR for having triple-negative tumors was 0.45 for AG/AA versus GG genotype (95% CI = 0.2-0.9, P = 0.02). We confirm the strong association between ATM rs56009889 and lung cancer risk in Ashkenazi Jews and report a mild association with the risk of breast cancer and colorectal cancer.

3 months ago

Journal

ATM (ATM serine/threonine kinase)

3ms

Primary Immunodeficiency-Type Ataxia-Telangiectasia Revealed by Splenic Abscesses. (PubMed, Cureus)

People suffering from this condition are particularly sensitive to ionizing radiation, which considerably increases their risk of developing neoplasia. We report an observation of a primary immunodeficiency-type A-T revealed by recurrent fever and multiple splenic abscesses.

3 months ago

Journal

ATM (ATM serine/threonine kinase)