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    BIOMARKER:

    RAD50 mutation

    i
    Other names: RAD50, RAD50 Double Strand Break Repair Protein, RAD50 Homolog Double Strand Break Repair Protein, DNA Repair Protein RAD50, RAD50 (S. Cerevisiae) Homolog, RAD50 Homolog (S. Cerevisiae), RAD502, HRad50, HRAD50, NBSLD
    Entrez ID:
    10111
    Related biomarkers:
    Mutation
    CNA
    1d
    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.
    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
    7d
    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
    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)
    2ms
    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)
    3ms
    CHANGEABLE: Combination of HX008 And Niraparib in GErm-line-mutAted Metastatic Breast Cancer (clinicaltrials.gov)
    P2, N=37, Completed, Fudan University | Recruiting --> Completed
    Trial completion • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BAP1 (BRCA1 Associated Protein 1) • 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) • 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) • WRN (WRN RecQ Like Helicase) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CDK12 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • HR positive + HER-2 negative • RAD50 mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • PTEN mutation + HR positive • CHEK1 expression • HER-2 negative + HR positive + BRCA mutation
    |
    Herceptin (trastuzumab) • Zejula (niraparib) • Puyouheng (pucotenlimab)
    3ms
    Clinical characteristics and genomic profiling of outpatients with endometrial cancer at a Chinese tertiary cancer center. (PubMed, Discov Oncol)
    Outpatients department gathered a considerable proportion of recurrent patients with complex genomic features. Patients with worse prognosis could be well studied, and anti-PD1 therapy was a promising salvage therapy in the real world.
    Journal • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • FANCA (FA Complementation Group A) • RAD50 (RAD50 Double Strand Break Repair Protein) • MUTYH (MutY homolog)
    |
    BRCA2 mutation • BRCA1 mutation • MSI-H/dMMR • MSH2 mutation • FANCA mutation • MLH1 mutation • RAD50 mutation
    3ms
    Identification of novel genetic variants associated with oral squamous cell carcinoma (OSCC) in South-West coast of India using targeted exome sequencing. (PubMed, Gene)
    Functional annotation and pathway analysis underscored the involvement of these mutated genes in various cancer-related pathways. Despite limitations such as sample size and the need for further validation, this study contributes to a deeper understanding of OSCC pathogenesis and highlights potential genetic markers for prognosis and targeted interventions, especially in the Indian context.
    Journal
    |
    TP53 (Tumor protein P53) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHD8 (Chromodomain Helicase DNA Binding Protein 8) • HNF1A (HNF1 Homeobox A)
    |
    TP53 mutation • RAD50 mutation
    8ms
    Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)
    P1, N=30, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting
    Enrollment open
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
    8ms
    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
    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)
    10ms
    Landscape of HRD aberration in EGFR mutated lung cancer and the role of PARP-inhibitor in EGFR mutated lung cancer with HRD aberration (AACR 2024)
    We also present a case demonstrating a favorable response to the dual therapy of olaparib and osimertinib in NSCLC harboring EGFR, RAD50, and ARID1A mutations that progressed on osimertinib. There were 2298 patients in the NSCLC cohort (MSKCC database). HRD aberrations are uncommon in EGFR mutated lung cancer patients. Further investigation on the role of PARP inhibitor in EGFR mutated lung cancer is warranted.
    PARP Biomarker • BRCA Biomarker
    |
    EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • RAD50 (RAD50 Double Strand Break Repair Protein)
    |
    BRCA2 mutation • BRCA1 mutation • EGFR mutation • EGFR exon 19 deletion • HRD • ARID1A mutation • EGFR E746_A750del • HRD + BRCA1 mutation • RAD50 mutation • EGFR E746
    |
    Guardant360® CDx
    |
    Lynparza (olaparib) • Tagrisso (osimertinib)
    10ms
    Evaluation of a Multimodal Strategy for Early Diagnosis of Men at High Genetic Risk of Prostate Cancer (HRPCa-II) (clinicaltrials.gov)
    P=N/A, N=880, Not yet recruiting, Assistance Publique - Hôpitaux de Paris | Trial completion date: Nov 2027 --> Jul 2029 | Trial primary completion date: Nov 2027 --> Jul 2029
    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)
    |
    BRCA1 mutation • PTEN mutation • PALB2 mutation • BRIP1 mutation • MSH2 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • BARD1 mutation • BLM mutation • MRE11A mutation • MLH3 mutation • NBN mutation
    10ms
    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
    Enrollment closed
    |
    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)
    10ms
    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)
    11ms
    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
    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)
    12ms
    SUKSES-B2: Olaparib and Bevacizumab in Relapsed Small Cell Lung Cancer Subjects (clinicaltrials.gov)
    P2, N=25, Completed, Se-Hoon Lee | Recruiting --> Completed | Trial primary completion date: Jun 2023 --> Oct 2023
    Trial completion • Trial primary completion date • Combination therapy
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • SLFN11 (Schlafen Family Member 11) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • WRN (WRN RecQ Like Helicase) • POU2F3 (POU Class 2 Homeobox 3) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
    |
    BRCA2 mutation • BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BLM mutation • BRCA mutation • MRE11A mutation • RAD54L mutation • NBN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation
    |
    Avastin (bevacizumab) • Lynparza (olaparib)
    1year
    Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)
    P1, N=30, Suspended, National Cancer Institute (NCI) | Initiation date: Oct 2023 --> Jul 2023
    Trial initiation date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
    1year
    High-grade serous ovarian carcinoma, the "Achiles' hill" for clinicians and molecular biologists: a molecular insight. (PubMed, Mol Biol Rep)
    For chemonaive patients, drugs that helps in efflux of reduced glutathione or prevent the redox coupling of GSH-GSSG, like Cisplatin, could be considered as the best therapeutic choice for HGSOC. For patients with BRCA1/2 mutations, PARP inhibitors alone or with Bevacizumab can be effective. Immune checkpoint inhibitors could be effective against immunoreactive subtypes. Identification of genes deregulated in chemoresistance could provide better insights in dealing with the disease.
    Review • Journal • BRCA Biomarker • PARP Biomarker • IO biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • FOXM1 (Forkhead Box M1) • MIR1290 (MicroRNA 1290) • MIR23A (MicroRNA 23a) • RASSF1 (Ras Association Domain Family Member 1) • MIR205 (MicroRNA 205)
    |
    TP53 mutation • BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • RAD50 mutation • PARP1 mutation • RAD51 mutation • RASSF1 methylation
    |
    Avastin (bevacizumab) • cisplatin
    1year
    The Largest Chinese Cohort Study Indicates Homologous Recombination Pathway Gene Mutations as Another Major Genetic Risk Factor for Colorectal Cancer with Heterogeneous Clinical Phenotypes. (PubMed, Research (Wash D C))
    Thus, germline mutation screenings should be performed for CRC patients with any of those genetic risk factors. This study also reveals that HR gene mutations may be another major driver for increased CRC risk.
    Journal
    |
    RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1)
    |
    ATM mutation • RAD50 mutation • BARD1 mutation
    1year
    Comprehensive genomic profiling (CGP) unravels somatic BRCA (sBRCA) and homologous recombinant repair (HRR) gene alterations across multi-cancer spectrum (ESMO Asia 2023)
    60% patients with sBRCA and HRR mutations treated with platinum / PARPi as NACT, achieved partial to pathological complete response (pCR) while 5 cases treated with IO are on follow up. Conclusions CGP identified sBRCA and HRR mutations in wide spectrum of cancers enabling the utility of PARPi as maintenance therapy, hence necessitating sBRCA and HRR testing as standard of care besides germline testing for personalized therapy.
    Tumor mutational burden • PARP Biomarker • BRCA Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • RAD50 (RAD50 Double Strand Break Repair Protein) • MRE11A (MRE11 homolog, double strand break repair nuclease)
    |
    BRCA1 mutation • RAD50 mutation • MRE11A mutation
    |
    TruSight Oncology 500 Assay
    1year
    Characterization of DNA Damage Response-Associated Somatic Mutations in Borderline Resectable and Locally Advanced Pancreatic Cancer. (PubMed, Int J Radiat Oncol Biol Phys)
    Herein, we characterized the frequency of somatic mutations associated with DSB repair genes in patients with BRPC/LAPC. Data analysis on outcomes related to radiation response in patients with mutations in DDR pathways is ongoing, but will likely also benefit from multi-institutional efforts to increase the power to answer this question.
    Journal • BRCA Biomarker • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PALB2 (Partner and localizer of BRCA2) • SMAD4 (SMAD family member 4) • RAD51B (RAD51 Paralog B) • RAD50 (RAD50 Double Strand Break Repair Protein) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)
    |
    TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDKN2A mutation • SMAD4 mutation • RAD50 mutation • RAD51B mutation • BLM mutation • RAD54L mutation • NBN mutation • PRKDC mutation • RAD51 mutation
    |
    FoundationOne® CDx
    |
    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium
    1year
    Comprehensive Genomic Analysis Stratified by KRAS Status in Patients with Pancreatic Adenocarcinoma and Its Prognostic Significance. (PubMed, Int J Radiat Oncol Biol Phys)
    This study identified driver mutations in patients with KRAS WT. KRAS status was associated with pathologic features and disease prognosis after treatment. Further study leveraging more powered cohorts is warranted.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • RAD50 (RAD50 Double Strand Break Repair Protein) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • AMER1 (APC Membrane Recruitment Protein 1) • BCORL1 (BCL6 Corepressor Like 1) • CDC73 (Cell Division Cycle 73)
    |
    KRAS mutation • BRAF mutation • KRAS wild-type • RAS wild-type • KRAS G12 • RAD50 mutation
    1year
    MRE11:p.K464R mutation mediates olaparib resistance by enhancing DNA damage repair in HGSOC. (PubMed, Cell Biosci)
    Our findings provide a theoretical basis for MRE11:p.K464R mutation as a specific indicator of resistance monitoring in Olaparib treatment, and the exploration of its resistance mechanism provides a novel insights for the formulation of combination ther therapies after Olaparib resistance.
    Journal • PARP Biomarker
    |
    RAD50 (RAD50 Double Strand Break Repair Protein) • MRE11A (MRE11 homolog, double strand break repair nuclease)
    |
    RAD50 mutation
    |
    Lynparza (olaparib)
    over1year
    Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)
    P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
    over1year
    Simultaneous Nbs1 and p53 inactivation in neural progenitors triggers High-Grade Gliomas (HGG). (PubMed, Neuropathol Appl Neurobiol)
    Our findings show that concomitant inactivation of Nbs1 and p53 in mice promotes HGG with RIG features. This model could be useful for preclinical studies to improve the prognosis of these deadly tumours, but it also highlights the singularity of NBS1 among the other DNA damage response proteins in the aetiology of brain tumours.
    Journal
    |
    RAD50 (RAD50 Double Strand Break Repair Protein)
    |
    RAD50 mutation
    over1year
    Characterization of DNA Damage Response-Associated Somatic Mutations in Borderline Resectable and Locally Advanced Pancreatic Cancer (ASTRO 2023)
    Chemotherapy consisted of modified FOLFIRINOX or gemcitabine/nab-paclitaxel, and patients were treated with SBRT in 33 Gy in 5 fractions... Herein, we characterized the frequency of somatic mutations associated with DSB repair genes in patients with BRPC/LAPC. Data analysis on outcomes related to radiation response in patie nts with mutations in DDR pathways is ongoing, but will likely also benefit from multi-institutional efforts to increase the power to answer this question .
    BRCA Biomarker • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PALB2 (Partner and localizer of BRCA2) • SMAD4 (SMAD family member 4) • RAD51B (RAD51 Paralog B) • RAD50 (RAD50 Double Strand Break Repair Protein) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)
    |
    TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDKN2A mutation • SMAD4 mutation • RAD50 mutation • RAD51B mutation • BLM mutation • RAD54L mutation • NBN mutation • PRKDC mutation • RAD51 mutation
    |
    FoundationOne® CDx
    |
    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium
    over1year
    Comprehensive Genomic Analysis Stratified by KRAS Status in Patients with Pancreatic Adenocarcinoma and Its Prognostic Significance (ASTRO 2023)
    This study identified driver mutations in patients with KRAS WT. KRAS status was associated with pathologic features and disease prognosis after treatment. Further study leveraging more powered cohorts is warranted.
    Clinical • Genomic analysis • Omic analysis
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • RAD50 (RAD50 Double Strand Break Repair Protein) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • AMER1 (APC Membrane Recruitment Protein 1) • BCORL1 (BCL6 Corepressor Like 1) • CDC73 (Cell Division Cycle 73)
    |
    KRAS mutation • BRAF mutation • KRAS wild-type • RAS wild-type • KRAS G12 • RAD50 mutation
    over1year
    HRD status of patients with early stage non-small cell lung cancer (ESMO 2023)
    Preliminary functional experiments in HRP (HR proficient, n=5) and HRD (n=4) PDX and organoids (n=3 and n=3 for HRD and HRP respectively) indicate that HRD tumors present low RAD51 foci count (p=0.03 after damage induction) and favorable response to Olaparib and CDDP. Conclusions These data suggest that homologous recombination may be deficient in a substantial proportion of early-stage NSCLC patients, supporting the potential use of PARPi in HRD patients in the adjuvant or maintenance setting.
    Clinical • PARP Biomarker • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • CHEK2 mutation • HRD + BRCA1 mutation • RAD50 mutation • CHEK1 mutation • CHEK1 expression
    |
    AmoyDx® HRD Focus Panel
    |
    Lynparza (olaparib)
    over1year
    Comprehensive genomic profiling of advanced HR+/HER2- breast cancer patients using liquid biopsy (ESMO 2023)
    Conclusions This study presents a comprehensive analysis of the mutational landscape of advanced HR+/HER2- breast cancer patients using liquid biopsy. Additionally, it compares the molecular profiles of patients with different clinical features receiving diverse treatments, thus identifying potential biomarkers for prognosis and targeted therapies.
    Clinical • BRCA Biomarker • Liquid biopsy • Metastases • Biopsy
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • FAT1 (FAT atypical cadherin 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
    |
    HER-2 negative • HER-2 mutation • RAD50 mutation
    |
    PredicineCARE™
    over1year
    Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)
    P1, N=30, Recruiting, National Cancer Institute (NCI) | Initiation date: Jul 2023 --> Oct 2023
    Trial initiation date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
    over1year
    Genomic profiles of renal cell carcinoma in a small Chinese cohort. (PubMed, Front Oncol)
    For ccRCC patients, mutations in VHL, PBRM1, BAP1, and SERD2 can reach 74%, 50%, 24%, and 18%, respectively, while for nccRCC patients, the most frequent mutation was FH (29%), MLH3 (24%), ARID1A (18%), KMT2D (18%), and CREBBP (18%)...Our study revealed that nccRCC is more heterogeneous than ccRCC. For nccRCC patients, the small panel shows a more clear profile of genetic characteristics by replacing MLH3, KMT2D, and CREBBP with ATM, MSH6, BRAF, and KRAS, which may help predict prognosis and make clinical decisions.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • KMT2D (Lysine Methyltransferase 2D) • MSH6 (MutS homolog 6) • VHL (von Hippel-Lindau tumor suppressor) • CREBBP (CREB binding protein) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • RAD50 (RAD50 Double Strand Break Repair Protein) • TFE3 (Transcription Factor Binding To IGHM Enhancer 3)
    |
    KRAS mutation • BRAF mutation • ATM mutation • ARID1A mutation • KMT2D mutation • PBRM1 mutation • BAP1 mutation • VHL mutation • RAD50 mutation • MLH3 mutation • TFE3 fusion
    |
    GDC-0927
    over1year
    Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)
    P1, N=30, Recruiting, National Cancer Institute (NCI) | Initiation date: Apr 2023 --> Jul 2023
    Trial initiation date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
    over1year
    Identification of New Potential Prognostic and Predictive Markers in High-Grade Osteosarcoma Using Whole Exome Sequencing. (PubMed, Int J Mol Sci)
    In particular, BRCA2 and RAD50 are involved in homologous recombination repair, and could thus be used as specific therapy targets of inhibitors of the enzyme Poly ADP Ribose Polymerase (PARP). Finally, tumor mutational burden is found to be a potential prognostic marker for OS.
    Journal • Tumor mutational burden • BRCA Biomarker • PARP Biomarker
    |
    TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • CREBBP (CREB binding protein) • RAD50 (RAD50 Double Strand Break Repair Protein)
    |
    ARID1A mutation • RAD50 mutation
    over1year
    Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer. (PubMed, Sci Rep)
    In conclusion, TP53 and PIK3CA mutations, as well as a higher ctDNA fraction, were associated with worse PFS with trastuzumab and cytotoxic chemotherapy. The enrichment of HRD-related gene mutations and newly detected variants in ctDNA may be related to resistance to treatment.
    Journal • BRCA Biomarker • Circulating tumor DNA • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein)
    |
    TP53 mutation • PIK3CA mutation • HRD • BRIP1 mutation • ERBB3 mutation • FANCA mutation • RAD50 mutation
    |
    Herceptin (trastuzumab) • DA 3111 (trastuzumab biosimilar)
    over1year
    Conventional Chondrosarcoma of the Rib Cage and Sternum: Clinicopathological and Molecular Analysis of 27 Patients Treated at a Single Institution. (PubMed, Hum Pathol)
    IDH mutant tumors are uncommon. Early diagnosis and margin-negative resection is treatment of choice since chondrosarcomas are chemo- and radioresistant.
    Journal
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • RAD50 (RAD50 Double Strand Break Repair Protein)
    |
    IDH1 mutation • RAD50 mutation
    over1year
    Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)
    P1, N=30, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting
    Enrollment open
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
    over1year
    The clinical value of homologous recombination deficiency score in prostate cancer. (ASCO 2023)
    In the 6 patients who received HRD-related treatments (including cisplatin based chemotherapy or olaparib), 1 of the 2 patients with low HRD score had PSA progression after 251 days (the other one was lost to follow up), while no PSA progression was observed in the 4 patients with high HRD score with a median follow-up of 107 days (range: 40-274 days). A mCRPC case with high HRD score (37) and HRR wild-type who received second line docetaxel+cisplatin even achieved undetectable PSA... To our knowledge, this is the first study in China reporting the association of HRD score and platinum-based treatments in PCa. Our results supported the possibility that HRD score could be predictive for the efficacy of platinum-based chemotherapy.
    Clinical • BRCA Biomarker • PARP Biomarker
    |
    TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • RB1 (RB Transcriptional Corepressor 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D)
    |
    TP53 mutation • BRCA2 mutation • HRD • ATM mutation • RB1 mutation • AR mutation • BRIP1 mutation • RAD51D mutation • RAD50 mutation • RAD51 mutation • High HRD score
    |
    Lynparza (olaparib) • cisplatin • docetaxel
    over1year
    The application of a multigene NGS assay in homologous recombination deficiency tracking. (ASCO 2023)
    A high rate of HR mutations was detected in ovarian, breast and prostate which is consistent with the PARPi approval in these tumor types. The presence of BRCA1/2 mutations was highly associated with increased LOH value whereas it did not correlate to other HR mutations. Additionally, the pancancer presence of HR gene alterations indicates that the use of such genes as biomarkers of platinum and PARPi treatments should be evaluated in a wider range of tumor types.
    Tumor mutational burden • PARP Biomarker • BRCA Biomarker • IO biomarker • Next-generation sequencing
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog 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)) • WRN (WRN RecQ Like Helicase)
    |
    TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • ARID1A mutation • PALB2 mutation • BAP1 mutation • BRIP1 mutation • RAD50 mutation • BARD1 mutation • BLM mutation • MRE11A mutation • NBN mutation • CHEK1 expression
    |
    OncoScan™ CNV Assay
    over1year
    Homologous recombination-related (HRR) gene mutations in patients with glioma and their relevance to genomic characteristics, tumor mutation burden (TMB), and prognosis. (ASCO 2023)
    This study showed HRR pathway genes status was significantly related to the genomic characteristics, TMB and prognosis of glioma patients. Compared to patients in HRR P/LP group, patients in Non-HRR P/LP group had higher mutation frequency of IDH1, lower TMB value and better prognosis. The relationship between HRR pathway genes and glioma needs to be further explored.
    Clinical • Tumor mutational burden • BRCA Biomarker
    |
    TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • DNMT3A (DNA methyltransferase 1) • MSH6 (MutS homolog 6) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD21 (RAD21 Cohesin Complex Component)
    |
    PTEN mutation • DNMT3A mutation • CHEK2 mutation • RAD50 mutation
    over1year
    Chemotherapeutic sensitivity in colorectal cancer expressing low RNA of wild type homologous recombination genes. (ASCO 2023)
    Background: Homologous recombination deficient (HRD) colorectal cancer (CRC) has improved overall survival (OS) when exposed to DNA damaging agents (DDA) oxaliplatin (OX) and irinotecan (IR). Here we report a novel subclass of CRC defined as patients with low RNA expressing WT HR genes that exhibit differential sensitivity to DDA. Significantly longer survival is noted in CRC with low expression BRCA1, RAD51 and BLM, while post-OX survival was significantly prolonged with low expression of BRCA1, BRIP1 and FANCA. Further characterization of sensitive HR genes will better predict DDA sensitivity and impact treatment sequencing.
    MSi-H Biomarker • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency) • DNMT3A (DNA methyltransferase 1) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ERCC1 (Excision repair cross-complementation group 1) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • WRN (WRN RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4)
    |
    BRCA1 mutation • BRIP1 mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • BRCA1 expression • FANCF mutation • NBN mutation
    |
    oxaliplatin • irinotecan
    over1year
    Multiregional Sequencing Analysis Reveals Extensive Genetic Heterogeneity in Gastric Tumors from Latinos. (PubMed, Cancer Res Commun)
    Our findings of a higher frequency of a poor prognosis associated molecular subtype in Latinos and a possible new aflatoxin gastric cancer etiology also advance cancer disparities research. Our study contributes to advancing our knowledge of gastric carcinogenesis, diagnostics, and cancer health disparities.
    Journal
    |
    RAD50 (RAD50 Double Strand Break Repair Protein) • FAT4 (FAT Atypical Cadherin 4) • FSIP2 (Fibrous Sheath Interacting Protein 2) • PCDHA1 (Protocadherin Alpha 1) • RECQL4( RecQ Like Helicase 4)
    |
    RAD50 mutation • RECQL4 mutation
    almost2years
    Prevalence of germline mutations in cancer susceptibility genes in Chinese patients with renal cell carcinoma. (PubMed, Transl Androl Urol)
    To our knowledge, this is the first report of pathogenic germline mutations in the FANCI and FANCM genes and heterozygous germline missense mutation in exon 5 of the FH gene c.563A>T:p.N188I in RCC. Young RCC patients, patients with bilateral or multifocal RCC, or patients with nccRCC are more likely to have pathogenic/potentially pathogenic germline mutations.
    Journal
    |
    SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FLCN (Folliculin)
    |
    RAD51C mutation • RAD50 mutation • NBN mutation • FANCI mutation • FANCM mutation
    almost2years
    Risk stratification and molecular heterogeneity of endometrial cancer and expression profile of TIM-3: A retrospective cohort study. (PubMed, Gynecol Oncol)
    Our study revealed the molecular heterogeneity across subtypes and subgroups. The new risk stratification system changed the risk grouping of some patients due to the integration of molecular features. RAD51B mutation can further stratify the recurrence risk in the p53wt subtype. Patients with MMRd or POLEmut may benefit most from immunotherapy against TIM-3.
    Retrospective data • Journal • IO biomarker
    |
    CD8 (cluster of differentiation 8) • JAK1 (Janus Kinase 1) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • RAD51B (RAD51 Paralog B) • RAD50 (RAD50 Double Strand Break Repair Protein)
    |
    TP53 mutation • TP53 wild-type • HAVCR2 expression • RAD50 mutation • RAD51B mutation • TP53 expression • RAD51 mutation
    almost2years
    Evaluation of the relationship between target expression and in vivo anti-tumor efficacy of AZD9592, an EGFR/c-MET targeted bispecific antibody drug conjugate (AACR 2023)
    Collectively, these results support the hypothesized mechanism of action of AZD9592: TOP1i induced tumor cell death due to formation of DNA DSB, and suggest opportunities in the treatment of tumors with a range of molecular features. AZD9592 is currently in a Phase 1 clinical trial in advanced solid malignancies.
    Preclinical
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • SLFN11 (Schlafen Family Member 11) • CASP3 (Caspase 3)
    |
    EGFR mutation • EGFR expression • EGFR wild-type • MET mutation • RAD50 mutation
    |
    tilatamig samrotecan (AZD9592)