News - CHEK2 mutation

Outcomes of a universal germline screening program in a community urology practice. (PubMed, Clin Genet)

Genetic risk assessment for high-risk individuals is feasible as part of a universal screening program in a community urology practice. Approximately 8% of tested patients were found to have pathogenic germline mutations, which is consistent with contemporary tertiary referral cohorts.

1 day ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

BRCA2 mutation • BRCA1 mutation • CHEK2 mutation • NBN mutation

ProstateNext®

Comprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO (clinicaltrials.gov)

P2, N=11, Active, not recruiting, Institut fuer Frauengesundheit | Recruiting --> Active, not recruiting | N=89 --> 11 | Trial primary completion date: Jan 2024 --> Jan 2025

1 day ago

Enrollment closed • Enrollment change • Trial primary completion date • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • XRCC2 (X-Ray Repair Cross Complementing 2) • FANCC (FA Complementation Group C) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

BRCA2 mutation • BRCA1 mutation • HER-2 amplification • HER-2 negative • HRD • ATM mutation • PALB2 mutation • ER positive + PGR positive • CHEK2 mutation • PGR positive • RAD51C mutation • RAD51D mutation • BARD1 mutation • RAD51 mutation

Keytruda (pembrolizumab) • Lynparza (olaparib)

11d

Variation Analysis in Premenopausal and Postmenopausal Breast Cancer Cases. (PubMed, J Pers Med)

These findings contribute to a deeper understanding of the underlying causes of breast cancer with respect to menopausal status. This study is the first from Turkey that reflects the molecular subtyping and somatic mutation profiles of breast cancer patients according to menopausal status.

11 days ago

Journal • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1) • CHEK2 (Checkpoint kinase 2) • ATR (Ataxia telangiectasia and Rad3-related protein)

HER-2 positive • TP53 mutation • PIK3CA mutation • PTEN mutation • ATR mutation • CHEK2 mutation

13d

Case report: Mutation evolution in a patient with TdT positive high grade B cell lymphoma with MYC and BCL2 rearrangements following the treatment of concurrent follicular lymphoma and diffuse large B-cell lymphoma. (PubMed, Discov Oncol)

This study reports a rare case of TdT positive "double hit" HGBL following the treatment of concurrent FL/DLBCL and highlights the mutation characteristics. Collectively, this study will help enrich the knowledge of TdT positive "double hit" HGBL transformed from FL/DLBCL.

13 days ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • FGFR3 (Fibroblast growth factor receptor 3) • CD20 (Membrane Spanning 4-Domains A1) • KMT2D (Lysine Methyltransferase 2D) • CHEK2 (Checkpoint kinase 2) • CREBBP (CREB binding protein) • BCL7A (BAF Chromatin Remodeling Complex Subunit BCL7A) • CCND3 (Cyclin D3) • MME (Membrane Metalloendopeptidase) • MUC4 (Mucin 4, Cell Surface Associated) • STAT6 (Signal transducer and activator of transcription 6) • ARID5B (AT-Rich Interaction Domain 5B) • DDX3X (DEAD-Box Helicase 3 X-Linked)

ATM mutation • MYC rearrangement + BCL2 rearrangement • KMT2D mutation • CHEK2 mutation • BCL2 expression • CD20 expression • MYC rearrangement • CD19 expression • BCL2 rearrangement • IGH translocation • BCL2 translocation

23d

Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors (clinicaltrials.gov)

P1, N=44, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting

23 days ago

Enrollment open • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • RAD50 mutation • CHEK1 mutation • CHEK1 expression

Cabometyx (cabozantinib tablet) • Partruvix (pamiparib)

24d

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

24 days ago

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

25d

Immunohistochemical Findings and Clinicopathological Features of Breast Cancers with Pathogenic Germline Mutations in Non-BRCA Genes. (PubMed, Hum Pathol)

With PTEN and CHEK2 pathogenic mutations, abnormal IHC patterns are seen in early atypical proliferative lesions. IHC may be applied to identify CHEK2 &PTEN mutated BCs and precursor lesions.

25 days ago

Journal • BRCA Biomarker

PTEN (Phosphatase and tensin homolog) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2)

ATM mutation • PTEN deletion • PTEN mutation • PALB2 mutation • CHEK2 mutation • ATM expression

Chromophobe Renal Cell Carcinoma With Extensive Retraction Artifact: A Potential Diagnostic Pitfall From Micropapillary Urothelial Carcinoma. (PubMed, Int J Surg Pathol)

Although the etiology behind the extensive stromal retraction in our tumors is unknown, this may likely be artifactual in nature. Nonetheless, it is important to include MPC-like chromophobe RCC in the spectrum of "variant" morphologies to avoid diagnostic pitfalls from micropapillary carcinoma.

1 month ago

Journal

TP53 (Tumor protein P53) • NF1 (Neurofibromin 1) • CHEK2 (Checkpoint kinase 2) • KRT7 (Keratin-7) • ZFHX3 (Zinc Finger Homeobox 3) • FLCN (Folliculin)

TP53 mutation • NF1 mutation • CHEK2 mutation

NIRADO: Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (clinicaltrials.gov)

P2, N=51, Suspended, Gustave Roussy, Cancer Campus, Grand Paris | N=112 --> 51 | Trial completion date: Mar 2027 --> Dec 2027 | Recruiting --> Suspended | Trial primary completion date: Mar 2024 --> Dec 2024

1 month ago

Enrollment change • Trial completion date • Trial suspension • Trial primary completion date • Pan tumor

HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • 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) • RAD51D (RAD51 paralog D) • ARID2 (AT-Rich Interaction Domain 2) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)

HER-2 positive • HER-2 amplification • DDR • PBRM1 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • NBN mutation • DRD

Zejula (niraparib) • Jemperli (dostarlimab-gxly)

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

1 month ago

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)

2ms

Ductal, intraductal, and cribriform carcinoma of the prostate: Molecular characteristics and clinical management. (PubMed, Urol Oncol)

Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.

2 months ago

Review • Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • RB1 (RB Transcriptional Corepressor 1) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • CHD1 (Chromodomain Helicase DNA Binding Protein 1) • MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7) • NKX3-1 (NK3 homeobox 1)

TP53 mutation • PTEN mutation • PALB2 mutation • CHEK2 mutation

docetaxel • abiraterone acetate

2ms

Association between missense variants of uncertain significance in the CHEK2 gene and hereditary breast cancer: a cosegregation and bioinformatics analysis. (PubMed, Front Genet)

However, the risk assessment for other variants is unclear. The incorporation of bioinformatics analysis provided supporting evidence of the pathogenicity of VUS.

2 months ago

Journal

CHEK2 (Checkpoint kinase 2)

CHEK2 mutation

2ms

Mainstream Model of Genetic Testing for Prostate Cancer at a Large Tertiary Cancer Centre. (PubMed, Clin Genitourin Cancer)

We report on the real-world characteristics of prostate cancer patients who underwent mainstream germline genetic testing. Personal history and family history of cancer cannot reliably stratify patients for the presence of pathogenic germline variants.

2 months ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • HOXB13 (Homeobox B13)

BRCA2 mutation • BRCA1 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • PMS2 mutation

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).

2 months ago

P2 data • Journal • BRCA Biomarker • PARP Biomarker • Metastases

ATM mutation • PALB2 mutation • CHEK2 mutation • RAD51 mutation

Rubraca (rucaparib)

2ms

ORCHID: Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations (clinicaltrials.gov)

P2, N=20, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Mar 2025

2 months ago

Trial completion date • Trial primary completion date • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)

BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression

Lynparza (olaparib)

2ms

Genetic mutation patterns among glioblastoma patients in the Taiwanese population - insights from a single institution retrospective study. (PubMed, Cancer Gene Ther)

In Taiwanese GBM patients, bevacizumab usage is linked to improved survival rates, affirming its safety and effectiveness...TP53 mutations are associated with enhanced survival, but their functional implications necessitate detailed exploration. This study pioneers genetic analysis in Taiwanese GBM patients using NGS, advancing our understanding of their genetic landscape.

2 months ago

Retrospective data • Journal

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CHEK2 (Checkpoint kinase 2)

TP53 mutation • EGFR mutation • CHEK2 mutation • IDH1 R132H • EGFR mutation + EGFR amplification • IDH1 R132

Avastin (bevacizumab)

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.

2 months ago

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

Relationship between the Expression of CHK2 and p53 in Tumor Tissue and the Course of Papillary Thyroid Cancer in Patients with CHEK2 Germline Mutations. (PubMed, Cancers (Basel))

Higher CHK2 expression was associated with poorer treatment responses and disease outcomes. Higher CHK2 expression and positive p53 together with a TP53 deletion could be a prognostic marker of unfavorable disease outcomes in patients with germline truncating mutations in CHEK2.

2 months ago

Journal

TP53 (Tumor protein P53) • CHEK2 (Checkpoint kinase 2)

TP53 mutation • TP53 deletion • CHEK2 mutation • TP53 expression

3ms

Germline CHEK2 mutations in patients with myeloid neoplasms. (PubMed, Leukemia)

No abstract available

3 months ago

Journal

CHEK2 (Checkpoint kinase 2)

CHEK2 mutation

3ms

A Study Evaluating Safety and Efficacy of Niraparib in Patients With Previously Treated Metastatic Esophageal/Gastroesophageal Junction/Proximal Gastric Adenocarcinoma (clinicaltrials.gov)

P2, N=43, Active, not recruiting, Shadia Jalal, MD | Trial completion date: Nov 2024 --> Jul 2024 | Trial primary completion date: Nov 2023 --> Feb 2023

3 months ago

Trial completion date • Trial primary completion date • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • CDK12 (Cyclin dependent kinase 12) • 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)) • RAD54L (DNA Repair And Recombination Protein RAD54) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • NBN mutation

Zejula (niraparib)

3ms

Germline mutations of homologous recombination genes and clinical outcomes in pancreatic cancer: a multicenter study in Taiwan. (PubMed, J Biomed Sci)

Our study showed that nearly 20% of Taiwanese PDAC patients carried germline P/LP variants. The longer survival observed in gHRmut patients treated with 1L platinum-based chemotherapy highlights the importance of germline testing for all patients with advanced PDAC at diagnosis.

3 months ago

Clinical • Clinical data • Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • FANCC (FA Complementation Group C)

BRCA1 mutation • ATM mutation • PALB2 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • FANCA mutation • BLM mutation • NBN mutation

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

3 months ago

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

A Study of Olaparib and Durvalumab in Prostate Cancer (clinicaltrials.gov)

P2, N=5, Terminated, Memorial Sloan Kettering Cancer Center | Completed --> Terminated; Due to low accrual

3 months ago

Trial termination • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)

BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • FANCA deletion

Lynparza (olaparib) • Imfinzi (durvalumab)

3ms

Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors (clinicaltrials.gov)

P1, N=44, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

3 months ago

Enrollment closed

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • RAD50 mutation • CHEK1 mutation • CHEK1 expression

Cabometyx (cabozantinib tablet) • Partruvix (pamiparib)

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

3 months ago

Enrollment closed

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)

3ms

Germline DNA Damage Response Gene Mutations in Localized Prostate Cancer. (PubMed, Medicina (Kaunas))

However, the number of cISUP > 1-grade patients with a CHEK2 mutation was significantly higher in advanced PCa than in localized PCa: 66.67% vs. 23.08% (p = 0.047). The results of our study suggest the potential of genetic screening for selected DDR gene mutations for early identification of cases at risk of aggressive PCa.

3 months ago

Journal • Tumor mutational burden • BRCA Biomarker

TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

ATM mutation • CHEK2 mutation • NBN mutation • BRCA2 mutation + ATM mutation

3ms

Phase IIB Trial of Bazedoxifene Plus Conjugated Estrogens (clinicaltrials.gov)

P2, N=120, Recruiting, University of Kansas Medical Center | Phase classification: P2b --> P2

3 months ago

Phase classification

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • NF1 (Neurofibromin 1) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

PTEN mutation • PALB2 mutation • CHEK2 mutation • NBN mutation

4ms

CHEK2 knockout is a therapeutic target for TP53-mutated hepatocellular carcinoma. (PubMed, Cell Death Discov)

Furthermore, MitoSox, electron microscopy, mitochondrial ATP, and NADH+/NADH levels were assessed in the CHEK2 knockout HCC cells with or without Metformin...Then we used MitoSox, electron microscopy, mitochondrial ATP, and NADH + /NADH assay and found knockout of CHECK could induce the ATP pathway to inhibit the growth of HCC. Our research introduces a novel drug target for TP53-mutant HCC cells via mitochondrial ATP, addressing the limitation of Nultin-3 as a standalone treatment that does not induce tumor cell death.

4 months ago

Journal

TP53 (Tumor protein P53) • CHEK2 (Checkpoint kinase 2)

TP53 mutation • CHEK2 mutation

metformin

4ms

OPTIMUM: Olaparib With or Without Durvalumab for DDR Gene Mutated Biliary Tract Cancer Following Platinum-based Chemotherapy (clinicaltrials.gov)

P2, N=62, Recruiting, Asan Medical Center | Trial completion date: Oct 2024 --> Dec 2025 | Trial primary completion date: Oct 2023 --> Dec 2024

4 months ago

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) • POLE (DNA Polymerase Epsilon) • BAP1 (BRCA1 Associated Protein 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • 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) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • XRCC2 (X-Ray Repair Cross Complementing 2) • FANCD2 (FA Complementation Group D2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)

ATM mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • FANCA mutation • RAD50 mutation • BARD1 mutation • BLM mutation • NBN mutation

Lynparza (olaparib) • Imfinzi (durvalumab)

4ms

Novel Pathogenic Variants in Hereditary Cancer Syndromes in a Highly Heterogeneous Cohort of Patients: Insights from Multigene Analysis. (PubMed, Cancers (Basel))

The implications of the study extend to personalized cancer prevention and treatment strategies, especially in populations lacking extensive epidemiological data, such as Russia. Overall, our research provides valuable genetic insights that give the way for further investigation and advances in the understanding and management of hereditary cancer syndromes.

4 months ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • EPCAM (Epithelial cell adhesion molecule) • MUTYH (MutY homolog)

BRCA2 mutation • BRCA1 mutation • ATM mutation • CHEK2 mutation • MLH3 mutation

4ms

Molecular and clinicopathological features of KIT/PDGFRA wild-type gastrointestinal stromal tumors. (PubMed, Cancer Sci)

NF1-GISTs involved multifocal spindle cell tumors in the small intestine. SDH-GISTs occurred in young patients and were multifocal in the stomach and clinically indolent.

4 months ago

Journal • Stroma

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • CHEK2 (Checkpoint kinase 2) • CREBBP (CREB binding protein) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

TP53 mutation • BRAF V600E • BRAF V600 • NF1 mutation • CHEK2 mutation • PDGFRA mutation • SDHB mutation • PDGFR wild-type

4ms

Pathogenic Germline Mutational Landscape in Patients With Renal Cell Carcinoma and Associated Clinicopathologic Features. (PubMed, JCO Precis Oncol)

Among patients with RCC, unselected for a known familial predisposition, 13.4% had P/LP variants. Almost half of patients with P/LP variants had a potentially targetable mutation. Targeted gene panel testing is a feasible option for patients, particularly if syndromic features are present. Age and family history were not associated with P/LP variants. Future studies are needed to optimize current genetic evaluation criteria to expand the detection of patients with RCC who may have germline mutations.

4 months ago

Journal

MLH1 (MutL homolog 1) • CHEK2 (Checkpoint kinase 2) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • FLCN (Folliculin)

CHEK2 mutation • SDHB mutation • FLCN mutation

5ms

Susceptibility Genes Associated with Multiple Primary Cancers. (PubMed, Cancers (Basel))

This review aims to discuss these susceptibility genes and provide an explanation of their functions based on the signaling pathway background. Additionally, the association network between genetic signatures and different tumor pairs will be summarized.

5 months ago

Review • Journal • BRCA Biomarker

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2)

TP53 mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • PTEN mutation • CHEK2 mutation • MSH2 mutation • MLH1 mutation

5ms

DIDO: Niraparib and Dostarlimab in HRD Solid Tumors (clinicaltrials.gov)

P2, N=30, Recruiting, West Cancer Center | Not yet recruiting --> Recruiting

5 months ago

Enrollment open • Combination therapy • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCI (FA Complementation Group I)

BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • FANCI mutation • RAD51 mutation

Zejula (niraparib) • Jemperli (dostarlimab-gxly)

5ms

CHEK2 deficiency increase the response to PD-1 inhibitors by affecting the tumor immune microenvironment. (PubMed, Cancer Lett)

Taken together, our results demonstrated that CHEK2 deficiency mutations may increase the response to ICB (eg. anti-PD-1) by influencing the tumor immune microenvironment. This indicated that CHEK2 deficiency mutations were a potentially predictive biomarker and CHEK2 deficiency may potentiate response to immunotherapy.

5 months ago

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

TMB (Tumor Mutational Burden) • POLE (DNA Polymerase Epsilon) • CD8 (cluster of differentiation 8) • CHEK2 (Checkpoint kinase 2)

POLE mutation • CHEK2 mutation

5ms

Germline mutations in pediatric cancer cohort with mixed-ancestry Mexicans. (PubMed, Mol Genet Genomic Med)

This report identifies potential genetic risk factors and provides a better understanding of the underlying mechanisms of childhood cancer in this population.

5 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • MSH6 (MutS homolog 6) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • MUTYH (MutY homolog) • DICER1 (Dicer 1 Ribonuclease III)

CDKN2A mutation • CHEK2 mutation • FANCA mutation

5ms

Real-world homologous recombination repair mutation (HRRm) testing patterns in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with olaparib in the United States. (ASCO-GU 2024)

Pts with confirmed mCRPC diagnosis, age â‰¥21 years, treated with olaparib monotherapy after exposure to abiraterone or enzalutamide, and with positive HRRm status were included. This real-world analysis highlights the need for earlier HRRm testing in pts with mCRPC to allow for optimal timing of novel treatment options that have shown efficacy in a biomarker-selected population. Most pts in this study were tested and diagnosed with HRRm many months after mCRPC diagnosis, at which point they had high levels of bone metastasis, multiple sites of distant metastases, and opioid use at the initiation of olaparib treatment. HRR testing in pts before or at the time of mCRPC would allow for olaparib therapy earlier in the disease course.

5 months ago

Real-world evidence • Clinical • PARP Biomarker • BRCA 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) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)

BRCA1 mutation • ATM mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression

Lynparza (olaparib) • Xtandi (enzalutamide capsule) • abiraterone acetate

5ms

The survival outcomes for men with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination deficiencies (HRD) treated with radium-223: Princess Margaret Cancer Centre (PMCC) experience. (ASCO-GU 2024)

A total of 29 (72.5%) patients received 233 Ra following abiraterone or enzalutamide treatment while 10 (25%) received 233 Ra post docetaxel. While the number of patients included in our review was small, our analysis suggested that patients with HRD may have a slight improvement in OS after 223Ra treatment. Validation in a prospective dataset is required, and whether HRD status has implications for other radiopharmaceuticals such as lutetium-177 remains to be seen.

5 months ago

BRCA Biomarker • Metastases

BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2)

HRD • CDK12 mutation • CHEK2 mutation

docetaxel • Xtandi (enzalutamide capsule) • abiraterone acetate • Xofigo (radium Ra-223 dichloride)

5ms

Homologous recombination repair gene mutation (HRRm) testing patterns and treatment selection from a real-world cohort of patients with metastatic castration-resistant prostate cancer (mCRPC). (ASCO-GU 2024)

31.7% (n=187) of tested patients were HRRm+ (11.2% germline (n=21); 73.8% somatic (n=138); 2.1% (n=4) germline + somatic; 12.8% (n=24) unknown), though not all tests utilized included the 14 HRR genes in the olaparib approval... In this real-world analysis, 40.8% of mCRPC patients did not receive germline or somatic testing while 33.2% of HRRm+ patients did not receive PARPi. Optimizing germline and somatic testing for mCRPC is a significant unmet need, which negatively impacts therapeutic offerings.

5 months ago

Clinical • Real-world evidence • BRCA Biomarker • PARP Biomarker • Real-world • Metastases

BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2)

CHEK2 mutation

Lynparza (olaparib)

5ms

Breast cancers in monoallelic MUTYH germline mutation carriers have clinicopathological features overlapping with those in BRCA1 germline mutation carriers. (PubMed, Breast Cancer Res Treat)

Although germline monoallelic MUTYH mutation is not thought to confer a meaningfully increased risk of breast cancer development, it may contribute to pathological aggressiveness and diversity of breast cancers when they sporadically arise in MUTYH carriers.

5 months ago

Journal • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • 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) • MUTYH (MutY homolog)

HER-2 positive • BRCA2 mutation • PALB2 mutation • CHEK2 mutation

5ms

Survival impact of homologous recombination deficiency in veterans with cholangiocarcinoma including mutual exclusivity with pathogenic KRAS and TP53. (ASCO-GI 2024)

Across a diverse integrated healthcare system of Veterans, mutations associated with HRD were found to be common, however, not prognostic in OS across a diverse patient population of CCA. Further work is needed to clarify exposure to platinum containing chemotherapy. TP53 MT CCA remains a critical unmet need that drives worsened outcomes including here in patients with mutations in HRD.

5 months ago

BRCA Biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

KRAS mutation • BRCA1 mutation • HRD • ATM mutation • ARID1A mutation • PALB2 mutation • CDK12 mutation • BAP1 mutation • CHEK2 mutation • HRD + BRCA1 mutation • BRCA mutation • NBN mutation

FoundationOne® CDx

5ms

Interactions between Iron Overload, Oxidative Stress, and Somatic Mutations in Myelodysplastic Syndromes; Evidence from the Literature (ASH 2023)

Of 31 mutations found in the IPSS-M, an additional four mutations found in familial predisposing conditions (DDX41, GATA2, CHEK2, SAMD9) were searched as was TET2, for a total of 35 mutations. Fifty-four references were identified. Fifty-three references were preclinical/translational in nature, with one case report (WT1).

5 months ago

Oxidative stress

TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • WT1 (WT1 Transcription Factor) • CHEK2 (Checkpoint kinase 2) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • STAG2 (Stromal Antigen 2) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • ERFE (Erythroferrone)

TP53 mutation • NRAS mutation • TET2 mutation • SF3B1 mutation • CBL mutation • CHEK2 mutation • U2AF1 mutation • STAG2 mutation