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GENE:

BARD1 (BRCA1 Associated RING Domain 1)

News alerts, weekly reports and conference planners

The breast tumor immune microenvironment of DNA double-strand break repair pathogenic variant carriers is enriched with tumor-associated macrophages. (PubMed, Cancer Epidemiol Biomarkers Prev)

These results support further characterization of macrophage characteristics and abundance in the breast tumor microenvironment of DSB repair-related pathogenic variant carriers.

5 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) • CHEK2 (Checkpoint kinase 2) • 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)) • FANCM (FA Complementation Group M) • STAT1 (Signal Transducer And Activator Of Transcription 1) • RECQL (RecQ Like Helicase) • FANCC (FA Complementation Group C)

16d

The combination of poly(ADP-ribose) polymerase inhibitor and statin inhibits the proliferation of human castration-resistant and taxane-resistant prostate cancer cells in vitro and in vivo. (PubMed, BMC Cancer)

Simvastatin altered the expression of several genes associated with DNA repair in castration-resistant and taxane-resistant prostate cancer cells. The combination of poly (ADP-ribose) polymerase inhibitors and drugs that decrease DNA repair gene expression can potentially affect castration-resistant and taxane-resistant prostate cancer growth.

16 days ago

Preclinical • Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BARD1 (BRCA1 Associated RING Domain 1) • FANCD2 (FA Complementation Group D2) • FANCG (FA Complementation Group G) • RFC4 (Replication Factor C Subunit 4)

Lynparza (olaparib) • cabazitaxel

18d

NCI10217: Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations (clinicaltrials.gov)

P1, N=39, Active, not recruiting, National Cancer Institute (NCI) | N=108 --> 39 | Trial completion date: Dec 2024 --> Mar 2026 | Trial primary completion date: Dec 2024 --> Jul 2024

18 days ago

Enrollment change • Trial completion date • Trial primary completion date

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • CD4 (CD4 Molecule) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

PIK3CA mutation • PTEN mutation • PALB2 mutation • CDK12 mutation • BARD1 mutation

Lynparza (olaparib) • Imfinzi (durvalumab) • Aliqopa (copanlisib)

20d

Targeting BARD1 suppresses a Myc-dependent transcriptional program and tumor growth in pancreatic ductal adenocarcinoma. (PubMed, Neoplasia)

Using a focused drug library of 477 DNA damage response compounds, we also found that BARD1 inhibition enhances therapeutic efficacy of several clinically relevant agents (fold changes ≥4), including PARPi, in HRR proficient PDAC cells. These data uncover BARD1 as an attractive therapeutic target for HRR proficient PDAC.

20 days ago

Journal

BRCA1 (Breast cancer 1, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • HRD (Homologous Recombination Deficiency) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • BARD1 (BRCA1 Associated RING Domain 1)

25d

Improving neuroblastoma risk prediction through a polygenic risk score derived from genome-wide association study-identified loci. (PubMed, Chin J Cancer Res)

Our findings validate multiple loci as neuroblastoma risk factors in Chinese children and demonstrate the utility of polygenic risk models, particularly the PRS, in improving risk prediction. These results suggest that integrating multiple genetic variants into a PRS can enhance neuroblastoma risk stratification and potentially improve early diagnosis by guiding targeted screening programs for high-risk children.

25 days ago

Journal

BARD1 (BRCA1 Associated RING Domain 1) • RSRC1 (Arginine And Serine Rich Coiled-Coil 1)

25d

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 2026 --> Mar 2028 | Trial primary completion date: Mar 2025 --> Mar 2027

25 days ago

Trial completion date • Trial primary completion date

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)

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

Lynparza (olaparib)

26d

Pathogenic germline variants in cancer predisposition genes in patients with multiple primary cancers in an Asian population and the role of extended panel genetic testing. (PubMed, ESMO Open)

Patients with MPC were more likely to harbour a PGV. Extended testing improved PGV detection rates, particularly for less well-known cancer predisposition genes.

26 days 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) • TET2 (Tet Methylcytosine Dioxygenase 2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase) • BARD1 (BRCA1 Associated RING Domain 1) • DDX41 (DEAD-Box Helicase 41) • FANCL (FA Complementation Group L) • CTNNA1 (Catenin Alpha 1) • RECQL4( RecQ Like Helicase 4) • SPINK1 (Serine peptidase inhibitor, kazal type 1) • CDKN1C (Cyclin Dependent Kinase Inhibitor 1C) • TNFRSF13B (TNF Receptor Superfamily Member 13B)

27d

Rare pathogenic structural variants show potential to enhance prostate cancer germline testing for African men. (PubMed, Nat Commun)

Notable African-specific loss-of-function gene candidates include DNA damage repair MLH1 and BARD1 and tumour suppressors FOXP1, WASF1 and RB1. Representing only a fraction of the vast African diaspora, this study raises considerations with respect to the contribution of kilo-to-mega-base rare variants to PCa pathogenicity and African-associated disparity.

27 days ago

Journal

RB1 (RB Transcriptional Corepressor 1) • MLH1 (MutL homolog 1) • BARD1 (BRCA1 Associated RING Domain 1) • FOXP1 (Forkhead Box P1)

SART3 promotes homologous recombination repair by stimulating DNA-RNA hybrids removal and DNA end resection. (PubMed, Nat Commun)

Moreover, SART3 promotes DNA end resection through enhancing USP15-BARD1 association and BRCA1-BARD1 retention. Together, our study reveals an role of SART3 in DSB repair, rendering SART3 a promising target for cancer therapy.

1 month ago

Journal

BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • BARD1 (BRCA1 Associated RING Domain 1) • DDX1 (DEAD-Box Helicase 1)

Reclassification of variants of uncertain significance by race, ethnicity, and ancestry for patients at risk for breast cancer. (PubMed, Front Oncol)

This study allows for improved and more equitable genetic counseling. It may also provide more reassurance to those groups that may have a higher likelihood of VUS results.

1 month ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • 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) • 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)

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 | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

1 month 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) • 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)

Genomic features of bladder neuroendocrine carcinoma with composite histology. (PubMed, Histol Histopathol)

Additionally, several cases harbored druggable gene alterations as presented by TMB-high. Our presentation of the histopathological and molecular features of NEC may help clarify the underlying mechanisms and contribute to efficient treatment of the disease.

1 month ago

Journal • Tumor mutational burden

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • RB1 (RB Transcriptional Corepressor 1) • BARD1 (BRCA1 Associated RING Domain 1)

TP53 mutation • TMB-H • PIK3CA mutation

Germline Mutations in Renal Neoplasms and Their Clinicopathological Correlations. (PubMed, Int J Surg Pathol)

Although they cannot be used to determine a definite renal entity, they may also contribute to the pathogenesis of renal neoplasms. Tumors need to be diagnosed based on morphology, immunohistochemistry, and other molecular evidence.

1 month ago

Journal

SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • TSC1 (TSC complex subunit 1) • BARD1 (BRCA1 Associated RING Domain 1) • MUTYH (MutY homolog) • FLCN (Folliculin)

BARD1 mutation

Causative Genes of Homologous Recombination Deficiency (HRD)-Related Breast Cancer and Specific Strategies at Present. (PubMed, Curr Oncol)

Therefore, a large-scale database, including clinical information and a long-term follow-up should be established, after which a periodical assessment is mandatory. The clinical behavior of each gene should be clarified based on a large-scale database, or, in other words, real-world data.

1 month ago

Review • Journal • BRCA Biomarker • PARP Biomarker

ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • BARD1 (BRCA1 Associated RING Domain 1)

HRD • BRCA mutation

The Emerging Role of the Histone H2AK13/15 Ubiquitination: Mechanisms of Writing, Reading, and Erasing in DNA Damage Repair and Disease. (PubMed, Cells)

Dysregulation of the precisely coordinated network of H2AK13/15ub is strongly associated with various diseases, including RIDDLE syndrome, neurodegenerative disorders, immune deficiencies, and breast cancer. This review systematically analyzes the dynamic regulation of H2AK13/15ub in DDR and explores its therapeutic potential for disease intervention.

1 month ago

Review • Journal

BRCA1 (Breast cancer 1, early onset) • BARD1 (BRCA1 Associated RING Domain 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1) • RNF168 (Ring Finger Protein 168)

Considerations for hereditary breast and ovarian cancer syndrome molecular diagnosis: experience from the clinical practice. (PubMed, Breast Cancer Res Treat)

Testing cancer susceptibility genes using an agnostic strategy confers a diagnostic benefit for hereditary cancer syndromes compared to phenotype-driven test, without adding complexity to the study. The analysis of healthy individuals with a family history of HBOC detects pathogenic variants in a cost-efficient percentage of cases, resulting in a good alternative strategy when the index case is unavailable.

1 month ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • 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)

The mutational landscape and its longitudinal dynamics in relapsed and refractory classic Hodgkin lymphoma. (PubMed, Ann Hematol)

This study delineates distinct mutational signatures between responders and rHL/prHL, whilst illustrating longitudinal dynamics in mutational profiles using paired samples. Further, several exploitable therapeutic vulnerabilities for rHL and prHL were identified.

1 month ago

Journal

MET (MET proto-oncogene, receptor tyrosine kinase) • NF1 (Neurofibromin 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PMS2 (PMS1 protein homolog 2) • ETV1 (ETS Variant Transcription Factor 1) • BARD1 (BRCA1 Associated RING Domain 1) • KAT6A (Lysine Acetyltransferase 6A) • EPHB1 (EPH Receptor B1)

BARD1 mutation

Genome sequencing enhances the diagnostic yield and expands the genetic landscape of male breast cancer. (PubMed, Genet Med Open)

Exome sequencing analysis further identified significant somatic oncogenic drivers and revealed a dominant mutational signature SBS3 across BRCA1/2-negative samples, reinforcing the contribution of omologous recombination deficiency underlying the MBC development. Our findings extended the MBC genetic spectrum beyond BRCA1/2 and highlighted the intricate interplay of monogenic and polygenic predispositions, presenting a comprehensive MBC genomic profile.

1 month ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • BARD1 (BRCA1 Associated RING Domain 1)

BARD1 mutation

2ms

Mutations in homologous recombination repair genes in patients with metastatic endometrial cancer: association with clinical characteristics and prognosis. (PubMed, J Gynecol Oncol)

Somatic HRR mutations are detected in 11.8% of metastatic EC. Compared with noncarriers, HRR mutation carriers in metastatic EC have higher proportions of endometrioid carcinoma, POLEmut, and dMMR subtypes, and unique metastatic patterns. However, the prognoses are similar regardless of HRR status.

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) • CDK12 (Cyclin dependent kinase 12) • 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)

TP53 mutation • MSI-H/dMMR • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation

2ms

Stand Up to Cancer: MAGENTA (Making Genetic Testing Accessible) (clinicaltrials.gov)

P=N/A, N=5200, Suspended, M.D. Anderson Cancer Center | Trial completion date: Apr 2024 --> Apr 2026 | Recruiting --> Suspended | Trial primary completion date: Apr 2024 --> Apr 2026

2 months ago

Trial completion date • Trial suspension • Trial primary completion date

ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)

PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation

2ms

Pembrolizumab, Olaparib, and Temozolomide for People with Glioma (clinicaltrials.gov)

P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

2 months ago

Trial completion date • Trial primary completion date

EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FGFR (Fibroblast Growth Factor Receptor) • CDK12 (Cyclin dependent kinase 12) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • 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)

CDKN2A deletion • BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type

Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide

2ms

Phase II Study of PARP Inhibitor Olaparib and IV Ascorbate in Castration Resistant Prostate Cancer (clinicaltrials.gov)

P2, N=4, Terminated, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=15 --> 4 | Trial completion date: Mar 2028 --> Oct 2024 | Recruiting --> Terminated | Trial primary completion date: Mar 2028 --> Oct 2024; The study was terminated by the IRB due to low accrual,

2 months ago

Enrollment change • Trial completion date • Trial termination • Trial primary completion date

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • FANCL (FA Complementation Group L)

FoundationOne® Liquid CDx

Lynparza (olaparib)

2ms

HRPCa-II: Evaluation of a Multimodal Strategy for Early Diagnosis of Men At High Genetic Risk of Prostate Cancer (clinicaltrials.gov)

P=N/A, N=880, Not yet recruiting, Assistance Publique - Hôpitaux de Paris | Trial completion date: Dec 2029 --> Mar 2030 | Trial primary completion date: Dec 2029 --> Mar 2030

2 months ago

Trial completion date • Trial primary completion date

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • HOXB13 (Homeobox B13)

PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation

2ms

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: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

2 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) • 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 • CHEK2 mutation • BRIP1 mutation • BARD1 mutation

Lynparza (olaparib) • Imfinzi (durvalumab)

2ms

RIOK1: A Novel Oncogenic Driver in Hepatocellular Carcinoma. (PubMed, Cancer Med)

Our findings suggest that RIOK1 is a novel oncogenic driver that may serve as a potential diagnostic and therapeutic target for HCC.

2 months ago

Journal

BARD1 (BRCA1 Associated RING Domain 1) • CCNA2 (Cyclin A2) • PMS1 (PMS1 protein homolog 1) • CCNB1 (Cyclin B1) • SMARCA5 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 5)

3ms

Niraparib and Dostarlimab for the Treatment of Germline or Somatic BRCA1/2 and PALB2 Mutated Metastatic Pancreatic Cancer (clinicaltrials.gov)

P2, N=22, Active, not recruiting, Mayo Clinic | Trial completion date: Sep 2024 --> Jun 2025

3 months ago

Trial completion date • IO biomarker

PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)

PD-L1 expression • PD-1 expression

Zejula (niraparib) • Jemperli (dostarlimab-gxly)

3ms

A portrait of germline pathogenic variants in high and moderate penetrance breast cancer genes in Brazil. (PubMed, Front Oncol)

Deleterious BRCA1/2 variants vary according to age and BC subtype. Our study gives a broader understanding of BC risk genes and has opened doors to optimized testing and surveillance strategies in Brazil.

3 months ago

Journal • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • 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) • 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)

ATM R337H

3ms

A Rare Case of a Malignant Proliferating Trichilemmal Tumor: A Molecular Study Harboring Potential Therapeutic Significance and a Review of Literature. (PubMed, Dermatopathology (Basel))

The confirmation of ERBB2 (HER2) amplification in the MPTT through a molecular analysis suggests potential therapeutic avenues involving anti-HER2 monoclonal antibodies. The presence of the TP53 mutation, without the concurrent gene mutations typically observed in SCC, significantly aided in this differential diagnosis.

3 months ago

Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • HRD (Homologous Recombination Deficiency) • PD-1 (Programmed cell death 1) • RUNX1 (RUNX Family Transcription Factor 1) • LRP1B (LDL Receptor Related Protein 1B) • GNA11 (G Protein Subunit Alpha 11) • KMT2C (Lysine Methyltransferase 2C) • TYMS (Thymidylate Synthetase) • MSH3 (MutS Homolog 3) • BARD1 (BRCA1 Associated RING Domain 1) • BRD4 (Bromodomain Containing 4) • HSPH1 (Heat Shock Protein Family H (Hsp110) Member 1)

PD-L1 expression • TP53 mutation • HER-2 amplification • HER-2 mutation • HER-2 expression • HRD • ATM mutation • TP53 expression • BARD1 mutation • HER-2 amplification + PD-L1 expression

3ms

Pembrolizumab, Olaparib, Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer (clinicaltrials.gov)

P1/2, N=71, Recruiting, Yonsei University | Not yet recruiting --> Recruiting | Trial completion date: May 2023 --> May 2025 | Trial primary completion date: Dec 2022 --> Dec 2024

3 months ago

Enrollment open • Trial completion date • Trial primary completion date

HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • 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)

HER-2 positive • BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression

Keytruda (pembrolizumab) • Lynparza (olaparib) • paclitaxel

4ms

High- and Moderate-Risk Variants Among Breast Cancer Patients and Healthy Donors Enrolled in Multigene Panel Testing in a Population of Central Russia. (PubMed, Int J Mol Sci)

The BLM, NBN, and MUTYH genes did not demonstrate associations with BC risk. Finding deleterious mutations in BC patients is important for diagnosis and management; in controls, it opens up the possibility of prevention and early diagnostics.

4 months ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • XRCC2 (X-Ray Repair Cross Complementing 2)

PALB2 mutation • RAD51C mutation • RAD50 mutation • BARD1 mutation • BLM mutation • NBN mutation

4ms

Comprehensive Clinical Genetics, Molecular and Pathological Evaluation Efficiently Assist Diagnostics and Therapy Selection in Breast Cancer Patients with Hereditary Genetic Background. (PubMed, Int J Mol Sci)

Further immunohistochemistry analysis of breast tumour tissues helped clarify the causative role of these variants. Comprehensive clinical and molecular genetic evaluation is beneficial for the diagnosis and management of patients with P/LP variants in hereditary tumour-predisposing genes and can serve as a basis for effective therapy selection, such as PARP inhibitors or immunotherapy.

4 months ago

Retrospective data • Journal • BRCA Biomarker • PARP Biomarker • IO biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • 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)

4ms

Niraparib in Tumors Metastatic to the CNS (clinicaltrials.gov)

P2, N=20, Recruiting, Massachusetts General Hospital | Trial completion date: Dec 2026 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Dec 2025

4 months ago

Trial completion date • Trial primary completion date • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BAP1 (BRCA1 Associated Protein 1) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • XRCC2 (X-Ray Repair Cross Complementing 2) • RAD54B (RAD54 Homolog B) • XRCC3 (X-Ray Repair Cross Complementing 3)

BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • BAP1 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • MRE11A mutation • RAD54L mutation • NBN mutation • HRD signature

Zejula (niraparib)

4ms

Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations (clinicaltrials.gov)

P2, N=36, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

4 months ago

Trial completion date • Trial primary completion date • Metastases

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) • BAP1 (BRCA1 Associated Protein 1) • 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) • 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)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • BACH1 (BTB Domain And CNC Homolog 1) • 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)

BRCA2 mutation • BRCA1 mutation • ATM mutation

Talzenna (talazoparib)

4ms

A phase II study evaluating safety and efficacy of niraparib in patients with previously treated homologous recombination defective metastatic esophageal/gastroesophageal junction/proximal gastric adenocarcinoma. (PubMed, Front Oncol)

The most common adverse events seen were anemia, fatigue, and thrombocytopenia. In patients with metastatic EAC, single agent niraparib as second line therapy is not an effective option.

4 months ago

P2 data • Journal • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • 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) • PARP2 (Poly(ADP-Ribose) Polymerase 2)

FANCA deletion

Zejula (niraparib)

4ms

Primary mucinous cystadenocarcinoma of the breast: A case report and literature review. (PubMed, Oncol Lett)

In conclusion, the current study presents a case of MCA of breast accompanied by mutations in the BARD1, KDR, MUC6, TP53 and BRIP1 genes, with no recurrence after a 26-month follow-up. Combining this case with a review of the literature helps us to better understand the clinicopathological and genetic characteristics of MCA, and guide treatment.

4 months ago

Review • Journal

TP53 (Tumor protein P53) • KDR (Kinase insert domain receptor) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MUC6 (Mucin 6)

TP53 mutation • BRIP1 mutation • BARD1 mutation

4ms

Functional profiling of murine glioma models highlights targetable immune evasion phenotypes. (PubMed, Acta Neuropathol)

Finally, we used a machine-learning approach to identify two distinct immune evasion gene programs, one of which represents a clinically-relevant phenotype and delineates a subpopulation of stem-like glioma cells that predict response to immune checkpoint inhibition in human patients. This comprehensive characterization helps bridge the gap between murine glioma models and human GBM, providing valuable insights for future therapeutic development.

4 months ago

Preclinical • Journal

BRCA1 (Breast cancer 1, early onset) • BARD1 (BRCA1 Associated RING Domain 1) • WWTR1 (WW Domain Containing Transcription Regulator 1) • PRRX1 (Paired Related Homeobox 1) • CENPA (Centromere protein A) • TCF4 (Transcription Factor 4)

5ms

Homologous recombination (HR) and DNA damage repair (DDR) somatic alterations in metastatic colorectal cancer (mCRC): results from the comprehensive genomic profiling (CGP) trial FPG500 (AIOM 2024)

Background : Treatment (tx) of MSS/MMRp mCRC relies mainly on oxaliplatin (oxa)- or irinotecan-based doublet chemotherapy regimens, with no biomarker reported so far, allowing the selection of one tx over the other. HR-DDRa is associated with MSI-H or TMB-H. Pts with MSS HR-DDRa tumors benefit from oxa-based first line treatment. Longer FU, allowing mature OS data, and wider cohorts are warranted.

5 months ago

Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • Metastases

TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

TMB-H • MSI-H/dMMR

TruSight Oncology 500 Assay

oxaliplatin • irinotecan

5ms

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.

5 months 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)

5ms

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

P1; Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Nov 2024 | Trial primary completion date: Dec 2025 --> Nov 2024

5 months ago

Trial completion date • Trial primary completion date • Trial completion

BRCA1 mutation • PALB2 mutation

MSK-IMPACT

cisplatin • gemcitabine

5ms

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

P1; Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

5 months ago

Trial completion date • Trial primary completion date • Metastases

BRCA1 mutation • PALB2 mutation

MSK-IMPACT

cisplatin • gemcitabine

6ms

Germline variants of homology-directed repair or mismatch repair genes in cervical cancer. (PubMed, Int J Cancer)

Taken together, our study supports a potentially risk-modifying role of MMR and HDR germline variants in cervical cancer but no association with HPV-negative status. These variants may be exploitable in future therapeutic managements.

6 months ago

Journal • Mismatch repair • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSH6 (MutS homolog 6) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • FANCM (FA Complementation Group M) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

6ms

Long Non-Coding RNA CRNDE, LINC00957, and AC072061.1 as a Promising Diagnostic and Prognostic Biomarker in Glioblastoma Multiforme. (PubMed, Iran J Public Health)

Altogether, we demonstrated lncRNA, and mRNA interaction and mentioned regulatory networks, considered a therapeutic option in GBM. In addition, we proposed potential diagnostic and prognostic biomarkers for the patients.

6 months ago

Journal

CDK6 (Cyclin-dependent kinase 6) • BARD1 (BRCA1 Associated RING Domain 1) • DBH-AS1 (DBH Antisense RNA 1) • CRNDE (Colorectal Neoplasia Differentially Expressed)