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    GENE:

    FANCL (FA Complementation Group L)

    i
    26d
    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
    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
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    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.
    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)
    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
    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,
    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)
    3ms
    Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects (clinicaltrials.gov)
    P2, N=30, Recruiting, Marc Dall'Era, MD | Trial completion date: Feb 2025 --> Jun 2025 | Trial primary completion date: Aug 2024 --> Jun 2025
    Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, 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) • CHEK1 (Checkpoint kinase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
    |
    Zejula (niraparib)
    3ms
    Whole genome and transcriptome analysis of pancreatic acinar cell carcinoma elucidates mechanisms of homologous recombination deficiency and unravels novel relevant fusion events. (PubMed, Pathol Res Pract)
    Additionally, we first describe structural variants in PACC, including BRCA1::TRIM47 fusion and another variant impacting FANCC, both events related to HRD, and we also identify alterations in the mitogen-activated protein kinase (MAPK) pathway, including RAF1 duplication as well as novel BRAF::SORBS2 and MAP7D2::SND1 gene fusions, offering potential targets for therapy. Our study underscores the importance of genome and transcriptome-wide profiling of PACC, to help guide personalized treatment strategies to improve patient outcomes.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRAF (B-raf proto-oncogene) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • FANCL (FA Complementation Group L) • SND1 (Staphylococcal Nuclease And Tudor Domain Containing 1) • FANCC (FA Complementation Group C) • TRIM47 (Tripartite Motif Containing 47)
    |
    HRD • FANCL mutation • BRCA1 fusion
    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
    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
    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
    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)
    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.
    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
    Luminal subtype independent immune-enrichment in inflammatory breast cancer based on commercially available tumor portrait. (SABCS 2024)
    Over half of cases with luminal molecular phenotype demonstrate immune-enriched TME, suggesting a potentially significant role for immunotherapy in these patients and expanded efforts in this arena. Using the BG Tumor PortraitTM assay, low TMB and MSS was present in the majority of IBC samples evaluated in spite of numerous studies showing common DNA repair mutations. HER2 expressing cases demonstrated a predominantly immune-desert phenotype and further study of the clinical relevance and validation of this is warranted.
    Tumor mutational burden • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • RAD51B (RAD51 Paralog B) • FANCL (FA Complementation Group L)
    |
    TP53 mutation • TMB-H • HR positive • HER-2 negative • PIK3CA mutation • HER-2 mutation • HER-2 expression • PTEN mutation • ARID1A mutation • TMB-L • RAD51B mutation
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay • BostonGene Tumor Portrait™ Test
    6ms
    Somatic gene mutations involved in DNA damage response/Fanconi anemia signaling are tissue- and cell-type specific in human solid tumors. (PubMed, Front Med (Lausanne))
    Furthermore, these gene alteration patterns significantly impact patient survival and disease-free periods. Collectively, our findings not only enhance our understanding of cancer development and progression but also have significant implications for cancer patient care and prognosis, particularly in the development of effective therapeutic strategies.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • XRCC2 (X-Ray Repair Cross Complementing 2) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • MAD2L2 (Mitotic Arrest Deficient 2 Like 2) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FAAP24 (FA Core Complex Associated Protein 24) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    |
    ATM mutation
    6ms
    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
    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)
    6ms
    A Risk Model Developed based on Homologous Recombination Deficiency Genes for Evaluating the Drug Sensitivity and Prognostic Prediction of Lung Adenocarcinoma. (PubMed, Curr Med Chem)
    The HRD-based RiskScore played a crucial role in LUAD development, showing a strong potential to serve as a prognostic indicator for LUAD. Our findings contributed to the diagnosis of LUAD and its treatment.
    Journal • BRCA Biomarker • IO biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A) • RAD51AP1 (RAD51 Associated Protein 1) • FANCL (FA Complementation Group L)
    |
    HRD
    7ms
    PARPi-PANC: Niraparib As First Line Therapy with Metastatic Homologous Repair-deficient Pancreatic Cancer (clinicaltrials.gov)
    P2, N=0, Withdrawn, Centre Leon Berard | N=28 --> 0 | Recruiting --> Withdrawn
    Enrollment change • Trial withdrawal • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCD2 (FA Complementation Group D2)
    |
    HRD signature
    |
    Zejula (niraparib)
    7ms
    Circulating Tumor DNA (ctDNA) Monitoring in the Assessment and Prediction of the Efficacy of PARP Inhibitors (PARPi) (clinicaltrials.gov)
    P=N/A, N=30, Recruiting, Sun Yat-sen University | Trial completion date: Aug 2023 --> Aug 2025
    Trial completion date • Circulating tumor DNA
    |
    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) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • BRCA1 mutation + ATM mutation • CHEK1 expression
    7ms
    Mesial temporal lobe epilepsy and hippocampal sclerosis associated with BRAFV600E mutant neurons in the Cornu Ammonis: an uncertain pathogenesis and a diagnostic challenge. (PubMed, Free Neuropathol)
    With next-generation sequencing, a FANCL deletion was detected in almost half of the alleles in our case, suggesting that many of the histologically normal-appearing cells of the hippocampus contain this alteration. FANCL mutations can result in cytogenetic anomalies and defective DNA repair and therefore may underlie the development of a low frequency BRAF alteration.
    Journal
    |
    BRAF (B-raf proto-oncogene) • CD34 (CD34 molecule) • FANCL (FA Complementation Group L)
    8ms
    DNA-Damaging Therapies in Patients With Prostate Cancer and Pathogenic Alterations in Homologous Recombination Repair Genes. (PubMed, JCO Precis Oncol)
    Patients with BRCA1/2-mutated PC had significantly improved outcomes to PARPi but not platinum chemotherapy compared with those with HRR mutations without direct BRCA complex interaction.
    Retrospective data • Journal • BRCA Biomarker • PARP Biomarker
    |
    HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • RAD54L2 (RAD54 Like 2)
    8ms
    NCI-2017-02296: Testing Olaparib in Patients With Advanced or Metastatic (Cancer That Has Spread) Bladder Cancer and Other Genitourinary Tumors With DNA-Repair Genetic Changes (clinicaltrials.gov)
    P2; Trial completion date: Aug 2024 --> Dec 2025 | Trial primary completion date: Aug 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Tumor mutational burden • Metastases
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1) • MSI (Microsatellite instability) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • POLE (DNA Polymerase Epsilon) • CCND1 (Cyclin D1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • POLD1 (DNA Polymerase Delta 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • BRD4 (Bromodomain Containing 4) • DOT1L (DOT1 Like Histone Lysine Methyltransferase) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • FANCC (FA Complementation Group C)
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    |
    Lynparza (olaparib)
    8ms
    A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors (clinicaltrials.gov)
    P1/2, N=120, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting | N=13 --> 120
    Enrollment open • Enrollment change
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • 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) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)
    9ms
    Homologous recombination (HR) and DNA damage repair (DDR) somatic alterations in metastatic colorectal cancer (mCRC): Results from the comprehensive genomic profiling (CGP) trial FPG500 (ESMO 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.
    Tumor mutational burden • MSi-H Biomarker • BRCA 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
    9ms
    E3 ligases: a ubiquitous link between DNA repair, DNA replication and human disease. (PubMed, Biochem J)
    Over the past two decades, numerous ubiquitin (Ub) E3 ligases have been identified to play a crucial role not only in the initiation of DNA replication and DNA damage repair but also in the efficient termination of these processes. In this review, we discuss our current understanding of how different Ub E3 ligases (RNF168, TRAIP, HUWE1, TRIP12, FANCL, BRCA1, RFWD3) function to regulate DNA repair and replication and the pathological consequences arising from inheriting deleterious mutations that compromise the Ub-dependent DNA damage response.
    Review • Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • FANCL (FA Complementation Group L) • HUWE1 (HECT UBA And WWE Domain Containing E3 Ubiquitin Protein Ligase 1) • TRIP12 (Thyroid Hormone Receptor Interactor 12) • RNF168 (Ring Finger Protein 168)
    10ms
    A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors (clinicaltrials.gov)
    P1/2, N=13, Suspended, National Cancer Institute (NCI) | N=120 --> 13 | Recruiting --> Suspended
    Enrollment change • Trial suspension
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • 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) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)
    10ms
    A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors (clinicaltrials.gov)
    P1/2, N=120, Recruiting, National Cancer Institute (NCI) | N=85 --> 120
    Enrollment change
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • 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) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)
    11ms
    Clinical actionability of BRCA2 alterations in uterine leiomyosarcoma: a molecular tumor board case report and a cBioPortal comprehensive analysis. (PubMed, Oncologist)
    uLMS displays a significant frequency of somatic BRCA2alt homDel. Considering their dismal prognosis, further investigation is warranted to test the use of PARPi in uLMS, and particularly in the setting of BRCA1/2 alterations.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • 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)) • 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)
    |
    BRCA2 mutation
    |
    Zejula (niraparib)
    12ms
    SMARCA4 Mutations in Gastroesophageal Adenocarcinoma: An Observational Study via a Next-Generation Sequencing Panel. (PubMed, Cancers (Basel))
    These results serve as the first comprehensive examination of the relationship between SMARCA4ms and clinical outcomes in GEA.
    Observational data • Journal • Next-generation sequencing • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • FANCA (FA Complementation Group A) • FANCL (FA Complementation Group L)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • HER-2 mutation • PTEN mutation • ARID1A mutation • SMARCA4 mutation
    1year
    BrUOG 360: A Study of Copanlisib Combined With Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=13, Active, not recruiting, Brown University | Trial completion date: May 2024 --> Jan 2027 | Trial primary completion date: Jan 2024 --> Jan 2027
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • 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) • 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)
    |
    BRIP1 mutation
    |
    Rubraca (rucaparib) • Aliqopa (copanlisib)
    1year
    New insights into the all-testis differentiation in zebrafish with compromised endogenous androgen and estrogen synthesis. (PubMed, PLoS Genet)
    The interaction between Fancl and Tp53 was observed via the WD repeat domain (WDR) and C-terminal domain (CTD) of Fancl and the DNA binding domain (DBD) of Tp53, leading to the K48-linked polyubiquitination degradation of Tp53 activated by the ubiquitin ligase, Fancl. Our results show that testis fate in cyp17a1-/- fish is determined by Dmrt1, which is thought to stabilize Tp53 by inhibiting fancl transcription during the critical stage of sexual fate determination in zebrafish.
    Journal
    |
    TP53 (Tumor protein P53) • CYP17A1 (Cytochrome P450 Family 17 Subfamily A Member 1) • FANCL (FA Complementation Group L) • DMRT1 (Doublesex And Mab-3 Related Transcription Factor 1)
    |
    CYP17A1 expression
    1year
    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
    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)
    1year
    Pembrolizumab, Olaparib, and Temozolomide for People With Glioma (clinicaltrials.gov)
    P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
    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
    1year
    TRIUMPH: Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (clinicaltrials.gov)
    P2, N=30, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    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)
    1year
    Digging into the NGS Information from a Large-Scale South European Population with Metastatic/Unresectable Pancreatic Ductal Adenocarcinoma: A Real-World Genomic Depiction. (PubMed, Cancers (Basel))
    About 28.41% showed PD-L1 > 1% either in tumor or immune cells, 15.75% expressed PD-L1 ≥ 10%, and only 1.18% had PD-L1 ≥ 50%. This is the largest depiction of real-world genomic characteristics of European patients with PDAC, which offers some useful clinical and research insights.
    Journal • Real-world evidence • Next-generation sequencing • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker • Real-world • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • SMAD4 (SMAD family member 4) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • FANCL (FA Complementation Group L) • FANCC (FA Complementation Group C)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • BRCA2 mutation • PALB2 mutation
    over1year
    Pembrolizumab, Olaparib, and Temozolomide for People With Glioma (clinicaltrials.gov)
    P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center
    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
    over1year
    DIDO: Niraparib and Dostarlimab in HRD Solid Tumors (clinicaltrials.gov)
    P2, N=30, Recruiting, West Cancer Center | Not yet recruiting --> Recruiting
    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)
    over1year
    Efficacy of olaparib (O) plus abiraterone (A) versus placebo (P) plus A in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with single homologous recombination repair gene mutations (HRRm) in the PROpel trial. (ASCO-GU 2024)
    BRCA2, ATM and CDK12 were the most prevalent single gene mutations and clinical benefit was observed with O + A. Other single gene mutations were rare, limiting interpretation. The greatest treatment benefit was observed in pts with BRCA mutations. Clinical trial information: NCT03732820.NR, not reached; BRIP1, RAD51B, RAD51D n=1; CHEK1, RAD51C n=0.
    Clinical • PARP Biomarker • BRCA Biomarker • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • 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 • CDK12 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BRCA mutation • CHEK1 mutation • BRCA2 mutation + ATM mutation • CHEK1 expression
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    |
    Lynparza (olaparib) • abiraterone acetate
    over1year
    Real-world effectiveness of PARP inhibitors (PARPi) in metastatic castration-resistant prostate cancer (mCRPC) by genomic homologous recombination repair (HRR) alterations and homologous recombination deficiency signature (HRDsig). (ASCO-GU 2024)
    We observe no significant outcomes difference between non-BRCAalt groups (defined as ATM, other HRR, and no HRR) in this cohort with respect to proxies of drug effectiveness. These results are largely consistent with biomarker-defined subgroup analyses from completed clinical trials. However, HRDsig may be able to identify a small non-BRCAalt subgroup with enhanced benefit.
    Clinical • Real-world evidence • BRCA Biomarker • PARP Biomarker • Real-world effectiveness • Real-world • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    BRCA2 mutation • HRD • HRD signature
    over1year
    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 ≥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.
    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) • abiraterone acetate
    over1year
    Molecular and immune landscape by cyclin dependent kinase (CDK) 4/6 expression and TP53 mutational status in mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). (ASCO-GI 2024)
    Our comprehensive analysis is the first to show distinct mutational profiles according to TP53 mut status, and differential expression of immune-related genes and TME cell infiltration independent of TP53 mut in CDK4/6 high vs low dMMR/MSI-H CRC. In our series, CDK6 expression correlated with ICI treatment benefit in TP53 mut tumors, warranting further studies to explore the potential of targeting the CDK4/6 axis to enhance ICI efficacy in CRC.
    Microsatellite instability • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker • Mismatch repair
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • DNMT3A (DNA methyltransferase 1) • ARID1A (AT-rich interaction domain 1A) • PD-1 (Programmed cell death 1) • KMT2A (Lysine Methyltransferase 2A) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • CDH1 (Cadherin 1) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • FANCL (FA Complementation Group L) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule) • HNF1A (HNF1 Homeobox A)
    |
    TP53 mutation • KRAS mutation • MSI-H/dMMR • BRAF mutation • ARID1A mutation • DNMT3A mutation • APC mutation • NF2 mutation • TP53 expression • MLL mutation • CDK4 mutation • CDK6 expression
    |
    MI Tumor Seek™
    over1year
    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 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
    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)
    over1year
    Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients. (PubMed, Open Med (Wars))
    Additionally, we found a correlation between DNA repair, cell cycle, and peroxide-related metabolic events and FA-related high/low risk or cluster 1/2. In summary, our novel FA-associated prognostic models promise to enhance the prediction of pediatric AML prognosis.
    Journal
    |
    FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • FANCL (FA Complementation Group L) • MAD2L2 (Mitotic Arrest Deficient 2 Like 2) • FANCC (FA Complementation Group C)
    over1year
    Development and introduction of methods for risk assessment and diagnosis of hereditary breast cancer in Armenia (ABC 2023)
    A hi-gh percentage of mutations in the sample indicates the relevance of this study. A unified database of frequencies of hereditary mutations in the genes of the DNA repair system for the population of Armenia will allow to assess the risks of hereditary breast cancer in Armenia, draw conclusions and develop appropriate recommendations.
    BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • 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) • EPCAM (Epithelial cell adhesion molecule) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    TP53 mutation • BRCA2 mutation • BRCA1 mutation • ATM mutation • CDH1 mutation
    over1year
    The role of DNA repair genes mutational status in prostate cancer treatment with androgen signaling blockade (EMUC 2023)
    Probably, the data obtained on the worst efficacy of enzalutamide after docetaxel in patients with mutations in  HRR genes can be attributed to the biological features of the influence of therapy methods on the course of the disease. In clinical practice, it is advisable to take into account the fact of the influence of previous treatment on the effectiveness of antiandrogenic therapy in choosing the sequence of treatment methods.
    BRCA Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • 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) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51B mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression
    |
    docetaxel • Xtandi (enzalutamide)
    over1year
    A Study of Niraparib in People With Soft Tissue Sarcoma Who Have Changes in Their Tumor DNA (clinicaltrials.gov)
    P2, N=8, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=32 --> 8
    Enrollment closed • Enrollment change
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • XRCC2 (X-Ray Repair Cross Complementing 2) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • RAD52 (RAD52 Homolog DNA Repair Protein) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • RAD23B (RAD23 Homolog B) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FANCC (FA Complementation Group C) • RAD54B (RAD54 Homolog B) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    |
    Zejula (niraparib)