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BIOMARKER:

RAD51B mutation

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Other names: RAD51 Paralog B, DNA Repair Protein RAD51 Homolog 2, RAD51 Homolog B, RAD51L1, R51H2, RAD51 Homolog B (S. Cerevisiae), RAD51 (S. Cerevisiae)-Like 1, RAD51-Like 1 (S. Cerevisiae), RAD51-Like Protein 1, RecA-Like Protein, Rad51B
Entrez ID:
Related biomarkers:
14d
LODESTAR: A Study to Evaluate Rucaparib in Patients With Solid Tumors and With Deleterious Mutations in HRR Genes (clinicaltrials.gov)
P2, N=83, Terminated, Clovis Oncology, Inc. | N=220 --> 83 | Active, not recruiting --> Terminated; The study was terminated due to a change in development priorities.
Enrollment change • Trial termination
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
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BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • NBN mutation • FANCA deletion • RAD51 mutation
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Rubraca (rucaparib)
21d
NCI-2021-12582: Niraparib for the Treatment of Leiomyosarcoma (clinicaltrials.gov)
P2, N=22, Not yet recruiting, David Liebner, MD | Initiation date: Apr 2022 --> Sep 2022
Trial initiation date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog 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)
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BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation
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Zejula (niraparib)
2ms
RAD51B Harbors Germline Mutations Associated With Pancreatic Ductal Adenocarcinoma. (PubMed, JCO Precis Oncol)
The finding in this study thus supports including RAD51B in the germline test of HR-DDR pathway genes.
Journal • BRCA Biomarker • BRCA Companion diagnostic
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • RAD51B (RAD51 Paralog B) • CHEK2 (Checkpoint kinase 2)
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BRCA2 mutation • HRD • PALB2 mutation • CHEK2 mutation • RAD51B mutation • RAD51 mutation • High HRD score
3ms
A Study Evaluating Safety and Efficacy of Niraparib in Patients With Previously Treated Metastatic Esophageal/Gastroesophageal Junction/Proximal Gastric Adenocarcinoma (clinicaltrials.gov)
P2, N=43, Recruiting, Shadia Jalal, MD | Trial completion date: May 2023 --> Nov 2024 | Trial primary completion date: May 2022 --> Nov 2023
Trial completion date • Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • CDK12 (Cyclin dependent kinase 12) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • NBN mutation
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Zejula (niraparib)
3ms
NEO: A Study of Olaparib Prior to Surgery and Chemotherapy in Ovarian, Primary Peritoneal, and Fallopian Tube Cancer (clinicaltrials.gov)
P2, N=71, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting | Trial completion date: Dec 2021 --> Dec 2024 | Trial primary completion date: Jun 2021 --> Dec 2022
Enrollment closed • Trial completion date • Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • RAD51D (RAD51 paralog D) • MUC16 (Mucin 16, Cell Surface Associated) • BARD1 (BRCA1 Associated RING Domain 1) • FANCM (FA Complementation Group M) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D)
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BRCA2 mutation • BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • FANCM mutation • MUC16 expression • PPM1D mutation • RAD51 mutation
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Lynparza (olaparib)
3ms
Concurrent BRAFV600E and BRCA Mutations in MSS Metastatic Colorectal Cancer: Prevalence and Case Series of mCRC patients with prolonged OS. (PubMed, Cancer Treat Res Commun)
Co-existence of BRAF V600E/BRCA1/2 may represent a unique subset of advanced MSS CRC that may have a better prognosis and represent an opportunity to test novel targeted therapies. The elevated gLOH in these cases may also be a valuable biomarker for these pts. Larger prospective clinical validation trials in this subset is warranted.
Journal • BRCA Biomarker • MSi-H Biomarker
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BRAF (B-raf proto-oncogene) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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BRAF V600E • BRCA2 mutation • BRCA1 mutation • MSI-H/dMMR • BRAF V600 • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • BRCA mutation • CHEK1 expression
4ms
M6620 (VX-970) in Selected Solid Tumors (clinicaltrials.gov)
P2, N=30, Completed, Massachusetts General Hospital | Active, not recruiting --> Completed
Trial completion
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCC (FA Complementation Group C)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • ARID1A mutation • MYC amplification • CDK12 mutation • CCNE1 amplification • ATRX mutation • FBXW7 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation
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OncoPanel™ Assay
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berzosertib (M6620)
5ms
LODESTAR: A Study to Evaluate Rucaparib in Patients With Solid Tumors and With Deleterious Mutations in HRR Genes (clinicaltrials.gov)
P2, N=220, Active, not recruiting, Clovis Oncology, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Mar 2023 --> Jun 2022 | Trial primary completion date: Dec 2022 --> May 2022
Enrollment closed • Trial completion date • Trial primary completion date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
|
BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • NBN mutation • FANCA deletion • RAD51 mutation
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Rubraca (rucaparib)
5ms
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 2023 --> Mar 2024 | Trial primary completion date: Mar 2022 --> Mar 2023
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) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • RAD51 mutation • CHEK1 expression
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Lynparza (olaparib)
5ms
Effects of homologous recombination-related gene mutation subtypes on gene instability and the efficacy of platinum-containing regiments in triple-negative breast cancer (AACR 2022)
In this study, we found that different HR-related genes mutation subtypes may exert distinct effects on genomic instability, and mutations in HR-related genes beyond the context of BRCA1/2 may serve as a biomarker for platinum-based adjuvant therapy for TNBC patients, which warrants further studies.
Clinical • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • HRD • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • HRD + BRCA1 mutation • RAD54L mutation • CHEK1 mutation • CHEK1 expression • High HRD score
5ms
Pan-cancer analysis revealed characteristics of reversion mutations in homologous recombination repair genes (AACR 2022)
This study analyzed clinical and mutational characteristics of reversion mutations in HRR genes, which could occur as single or multiple variants to restore the function of predisposed pathogenic HRR mutations, resulting in resistance to platinum-based chemotherapies or PARP inhibitors. Monitoring these mutations with tissue or liquid biopsy samples are crucial for treatment guidance.
BRCA Biomarker • PARP Biomarker • Pan tumor
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • WRN (WRN RecQ Like Helicase) • FANCD2 (FA Complementation Group D2) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit) • FANCC (FA Complementation Group C)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • MRE11A mutation • RAD54L mutation • BLM mutation • CHEK1 mutation • NBN mutation • WRN mutation • FANCI mutation • CHEK1 expression
6ms
Trial completion date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • CHEK1 expression
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FoundationOne® CDx
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berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)
6ms
PROspect: The Study of Olaparib in Newly Diagnosed mCRPC Patients With HRR Gene Mutation (clinicaltrials.gov)
P2, N=30, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
New P2 trial
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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PALB2 mutation • CDK12 mutation • ATRX mutation • BRIP1 mutation • CHEK2 mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression
|
Lynparza (olaparib)
6ms
Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
P2, N=50, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2022 --> Feb 2023 | Trial primary completion date: Jan 2022 --> Sep 2022
Trial completion date • Trial primary completion date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
|
Lynparza (olaparib)
6ms
NCI-2021-12582: Niraparib for the Treatment of Leiomyosarcoma (clinicaltrials.gov)
P2, N=22, Not yet recruiting, Ohio State University Comprehensive Cancer Center | Initiation date: Jan 2022 --> Apr 2022
Trial initiation date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog 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)
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BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation
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Zejula (niraparib)
7ms
Niraparib in Tumors Metastatic to the CNS (clinicaltrials.gov)
P2, N=20, Recruiting, Massachusetts General Hospital | Not yet recruiting --> Recruiting
Enrollment open
|
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) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • XRCC2 (X-Ray Repair Cross Complementing 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54B (RAD54 Homolog B) • XRCC3 (X-Ray Repair Cross Complementing 3)
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BRCA1 mutation • ATM mutation • HRD • PALB2 mutation • BAP1 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • HRD + BRCA1 mutation • MRE11A mutation • RAD54L mutation • NBN mutation
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Zejula (niraparib)
7ms
Pembrolizumab, Olaparib, and Temozolomide for People With Glioma (clinicaltrials.gov)
P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center | Not yet recruiting --> Recruiting
Enrollment open
|
EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • FGFR (Fibroblast Growth Factor Receptor) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type
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Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide
7ms
LODESTAR: A Study to Evaluate Rucaparib in Patients With Solid Tumors and With Deleterious Mutations in HRR Genes (clinicaltrials.gov)
P2, N=220, Recruiting, Clovis Oncology, Inc. | Trial completion date: May 2022 --> Mar 2023 | Trial primary completion date: Nov 2021 --> Dec 2022
Trial completion date • Trial primary completion date
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
|
BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • NBN mutation • FANCA deletion • RAD51 mutation
|
Rubraca (rucaparib)
7ms
Pembrolizumab, Olaparib, and Temozolomide for People With Glioma (clinicaltrials.gov)
P2, N=57, Not yet recruiting, Memorial Sloan Kettering Cancer Center
Clinical • New P2 trial
|
EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • FGFR (Fibroblast Growth Factor Receptor) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type
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Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide
7ms
Clinical • Trial completion
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • MUC16 (Mucin 16, Cell Surface Associated) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA2 mutation • BRCA1 mutation • CHEK2 mutation • RAD51B mutation • BARD1 mutation • BRCA mutation
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Lynparza (olaparib)
7ms
ADAM: A multicenter, non-interventional, prospective cohort study for determination of prevalence of homologous recombination repair genes mutations (HRRm) in metastatic castrate resistant prostate cancer (mCRPC)—Interim analysis. (ASCO-GU 2022)
This first systematic analysis of HRRm in Russian population of mCRPC patients showed general consistency with previously reported HRRm data (19,7% in our trial in comparison with 27.9% in PROfound trial). Lab approach using different techniques in real practice has to be established.
Clinical • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • RAD51 mutation
7ms
DNA damaging therapies in patients (pts) with prostate cancer (PC) and pathogenic alterations in homologous recombination repair (HRR) genes. (ASCO-GU 2022)
PC pts with BRCA1/2 mutations had improved outcomes to PARPi compared to those with mutations in HRR genes not directly interacting with the BRCA complex. Platinum-based chemo appeared effective regardless of which HRR gene was affected. Outcomes to DNA damaging therapies.
Clinical • BRCA Biomarker • PARP Biomarker
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HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRCA (Breast cancer early onset) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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BRCA2 mutation • BRCA1 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • FANCA mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • CHEK1 expression
8ms
NCI-2021-12582: Niraparib for the Treatment of Leiomyosarcoma (clinicaltrials.gov)
P2, N=22, Not yet recruiting, Ohio State University Comprehensive Cancer Center
New P2 trial
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog 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)
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BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation
|
Zejula (niraparib)
8ms
New P2 trial
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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PALB2 mutation • CDK12 mutation • ATRX mutation • BRIP1 mutation • CHEK2 mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression
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Lynparza (olaparib) • abiraterone acetate • prednisone
8ms
Homologous Recombination Deficiency (HRD) Mutations in Advanced Prostate Cancer: A Clinicopathologic Study of 17 Cases from an Indian Perspective (USCAP 2022)
Ours is the first Indian study evaluating HRD mutations in PC demonstrating the same in about one-third of the patients. HRD mutations were more prevalent in tumors with high Gleasons score and group grade. Given the recent FDA approval for two PARP inhibitors, the presence of defects in HRR pathway suggest that these patients could benefit from targeted therapy and can be included in the neoadjuvant clinical trials.
Clinical • BRCA Biomarker • PARP Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • AR (Androgen receptor) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MRE11A (MRE11 homolog, double strand break repair nuclease) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCD2 (FA Complementation Group D2)
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TP53 mutation • BRCA2 mutation • ATM mutation • HRD • BRIP1 mutation • RAD51B mutation • BARD1 mutation • NBN mutation
9ms
Local features of penetrant mutations incidence in patients with prostate cancer in Republic of Bashkortostan (EMUC 2021)
The frequency of mutations in repair gene is characterized by territorial features. The frequency of determining pathogenic mutations in the genes in question was determined.
Clinical • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation
9ms
New trial • Circulating tumor DNA
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • CHEK1 expression
10ms
Whole-Genome Sequencing Reveals Comprehensive Genomic Profiles of Radiation-Induced Sarcomas. (PubMed, Int J Radiat Oncol Biol Phys)
Taken together, WGS-scale characterization of RIS genomes may pave the way for advanced diagnostic and therapeutic strategies for RIS.
Journal
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • NF1 (Neurofibromin 1) • NOTCH2 (Notch 2) • RAD51B (RAD51 Paralog B) • ARID1B (AT-Rich Interaction Domain 1B)
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PIK3CA mutation • NF1 mutation • CDKN2A mutation • RAD51B mutation
11ms
A Study Evaluating Safety and Efficacy of Niraparib in Patients With Previously Treated Metastatic Esophageal/Gastroesophageal Junction/Proximal Gastric Adenocarcinoma (clinicaltrials.gov)
P2, N=43, Recruiting, Shadia Jalal, MD | Trial completion date: May 2022 --> May 2023 | Trial primary completion date: May 2021 --> May 2022
Clinical • Trial completion date • Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • CDK12 (Cyclin dependent kinase 12) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • NBN mutation
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Zejula (niraparib)
11ms
ORZORA: To Assess the Efficacy and Safety of Olaparib Maintenance Monotherapy in the Treatment of Ovarian Cancer (clinicaltrials.gov)
P4, N=181, Active, not recruiting, AstraZeneca | Trial completion date: Jun 2021 --> Sep 2021
Clinical • Trial completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • MUC16 (Mucin 16, Cell Surface Associated) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA2 mutation • BRCA1 mutation • CHEK2 mutation • RAD51B mutation • BARD1 mutation • BRCA mutation
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Lynparza (olaparib)
11ms
Enrollment open
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • CHEK1 expression
|
FoundationOne® CDx
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berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)
12ms
Pembrolizumab, Olaparib, Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer With HRR Mutation and MSS (clinicaltrials.gov)
P1/2, N=71, Not yet recruiting, Yonsei University | Trial completion date: Dec 2022 --> May 2023 | Initiation date: May 2021 --> Oct 2021 | Trial primary completion date: Jul 2022 --> Dec 2022
Clinical • Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy
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HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • MSH6 (MutS homolog 6) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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HER-2 positive • BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
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Keytruda (pembrolizumab) • Lynparza (olaparib) • paclitaxel
12ms
SUKSES-B2: Olaparib and Bevacizumab in Relapsed Small Cell Lung Cancer Subjects (clinicaltrials.gov)
P2, N=28, Recruiting, Se-Hoon Lee | Not yet recruiting --> Recruiting
Clinical • Enrollment open • Combination therapy
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • SLFN11 (Schlafen Family Member 11) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD54L (DNA Repair And Recombination Protein RAD54) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • WRN (WRN RecQ Like Helicase) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
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BRCA2 mutation • BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • MRE11A mutation • RAD54L mutation • BLM mutation • BRCA mutation • NBN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation
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Avastin (bevacizumab) • Lynparza (olaparib)
1year
Niraparib in Tumors Metastatic to the CNS (clinicaltrials.gov)
P2, N=20, Not yet recruiting, Massachusetts General Hospital
New P2 trial
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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) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • XRCC2 (X-Ray Repair Cross Complementing 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
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BRCA1 mutation • ATM mutation • HRD • PALB2 mutation • BAP1 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • HRD + BRCA1 mutation • MRE11A mutation • RAD54L mutation • NBN mutation
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Zejula (niraparib)
1year
DIDO: Niraparib and Dostarlimab in HRD Solid Tumors (clinicaltrials.gov)
P2, N=30, Not yet recruiting, West Cancer Center
New P2 trial
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCI (FA Complementation Group I)
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BRCA1 mutation • ATM mutation • HRD • PALB2 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • HRD + BRCA1 mutation • RAD54L mutation • FANCI mutation • RAD51 mutation
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Zejula (niraparib) • Jemperli (dostarlimab)
1year
Clinical • New P2 trial
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • ATM mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • ATM positive
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docetaxel • senaparib (IMP4297)
1year
Clinical • New P2 trial • Combination therapy
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • SLFN11 (Schlafen Family Member 11) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD54L (DNA Repair And Recombination Protein RAD54) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • WRN (WRN RecQ Like Helicase) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
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BRCA2 mutation • BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • MRE11A mutation • RAD54L mutation • BLM mutation • BRCA mutation • NBN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation
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Avastin (bevacizumab) • Lynparza (olaparib)
1year
Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
P2, N=50, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2022 --> Aug 2022 | Trial primary completion date: Aug 2021 --> Jan 2022
Trial completion date • Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
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Lynparza (olaparib)
over1year
[VIRTUAL] Frequency of homologous recombination repair alterations in ovarian cancer in Chinese population. (ASCO 2021)
CtDNA can characterize the mutational feature of HRR in OC . Around 42.3% of patients with OC harbour germline or somatic HRR mutations . The expanded use of PARP inhibitors in HRR deficient tumours using a signature of HRR by ctDNA in clinical practice requires validation.
Clinical • BRCA Biomarker • PARP Biomarker
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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) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54)
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BRCA1 mutation • ATM mutation • PALB2 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • RAD54L mutation • CHEK1 mutation • RAD51 mutation • CHEK1 expression
over1year
[VIRTUAL] Laboratory cross-comparison of homologous recombination repair mutation analysis in tumor in a multicenter epithelial ovarian cancer series: The BORNEO GEICO 60-0 study. (ASCO 2021)
In our EOC series the concordance of two Laboratories in the identification of clinically relevant HRR mutations on tumor is high but discrepancies in interpretation remain a challenge that needs further harmonization.
Clinical • BRCA Biomarker • PARP Biomarker
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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) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD51 mutation • CHEK1 expression
over1year
[VIRTUAL] Frequency of homologous recombination deficiency gene mutations in melanoma and its relevance to the immunotherapeutic response. (ASCO 2021)
Our data suggest that detection of somatic mutations in HRR genes might contribute to identify patients who might benefit from immune checkpoint blockade therapy . In addition, the molecular features of HRD provide new opportunities to predict the tumor response to multiple treatments.
BRCA Biomarker • IO biomarker
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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) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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BRCA1 mutation • ATM mutation • HRD • PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • HRD + BRCA1 mutation • CHEK1 expression
over1year
[VIRTUAL] Landscape of homologous recombination-related (HRR) genes mutations in colon cancer. (ASCO 2021)
Our data suggest that detection of somatic mutations in HRR genes might contribute to identify patients who might benefit from immune checkpoint blockade therapy and PARP inhibitors . In addition, the molecular features of HRR provide new opportunities to predict the tumor response to multiple treatments . Exploring other biomarkers of HRD to predict the response to PARPi and immunotherapeutic in colon cancer is necessary.
Tumor Mutational Burden • BRCA Biomarker • MSi-H Biomarker • PARP Biomarker • IO biomarker
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TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • CD8 (cluster of differentiation 8) • PALB2 (Partner and localizer of BRCA2) • IFNG (Interferon, gamma) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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BRCA2 mutation • MSI-H/dMMR • ATM mutation • HRD • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51B mutation • BARD1 mutation • RAD51 mutation • CHEK1 expression
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MSK-IMPACT
over1year
[VIRTUAL] Analysis of circulating tumor DNA identifies homologous recombination repair molecular features of Chinese breast cancer. (ASCO 2021)
CtDNA can characterize the mutational feature of HRR in BC . our study contributes to the understanding of the HRR pathways and specific genetic alterations harbored by Chinese patients with BC that could potentially be developed as markers of treatment response to targeted therapeutics . Ref: Razavi P, Chang MT, Xu GT, et al .
BRCA Biomarker • PARP Biomarker • Circulating tumor DNA
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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) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • RAD51 mutation • CHEK1 expression
over1year
[VIRTUAL] Concurrent BRAFV600E and BRCA mutations in microsatellite stable (MSS) metastatic colorectal cancer (mCRC): Prevalence and case series of mCRC (pts) with prolonged overall survival (OS). (ASCO 2021)
Co-existence of BRAF V600E/BRCA1/2 may represent a unique subset of advanced MSS CRC that may have a better prognosis and represent an opportunity to test novel targeted therapies . Larger prospective clinical validation trials in this subset is warranted.
Clinical • MSi-H Biomarker • BRCA Biomarker
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BRAF (B-raf proto-oncogene) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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BRAF V600E • BRCA2 mutation • BRCA1 mutation • MSI-H/dMMR • BRAF V600 • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • BRCA mutation • CHEK1 expression
over1year
Pembrolizumab, Olaparib, Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer With HRR Mutation and MSS (clinicaltrials.gov)
P1/2, N=71, Recruiting, Yonsei University | Not yet recruiting --> Recruiting | Initiation date: Dec 2020 --> May 2021
Clinical • Enrollment open • Trial initiation date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • MSH6 (MutS homolog 6) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • 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 • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
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Keytruda (pembrolizumab) • Lynparza (olaparib) • paclitaxel
over1year
Long-term survival of an ovarian cancer patient harboring a RAD51C missense mutation. (PubMed, Cold Spring Harb Mol Case Stud)
Conversely, its position within a critical site suggests that it is refractory to secondary mutations that would restore RAD51C gene function and lead to therapy resistance. A need for a greater understanding of the relationship between mutation position and reversion potential of HR genes is underscored, as it may help predict the effectiveness of therapies in patients with HR-deficient cancers.
Clinical • Journal
|
RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • XRCC2 (X-Ray Repair Cross Complementing 2)
|
RAD51C mutation • RAD51D mutation • RAD51B mutation • RAD51 mutation
over1year
Tumor genomic, transcriptomic, and immune profiling characterizes differential response to first-line platinum chemotherapy in high grade serous ovarian cancer. (PubMed, Cancer Med)
Our research demonstrates that tumors from HGSOC patients responding poorly to first line chemotherapy have a distinct molecular profile characterized by actionable drug targets including PARP4.
Clinical • Journal • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
|
PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • RAD51B (RAD51 Paralog B) • MECOM (MDS1 And EVI1 Complex Locus) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)
|
PD-L1 expression • BRCA2 mutation • PIK3CA mutation • PIK3CA amplification • RAD51B mutation • RAD51 mutation
|
carboplatin • paclitaxel
over1year
New P1/2 trial
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
|
BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • CHEK1 expression
|
FoundationOne® CDx
|
berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)
over1year
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 2022 --> Mar 2023 | Trial primary completion date: Mar 2021 --> Mar 2022
Clinical • 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) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • RAD51 mutation • CHEK1 expression
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Lynparza (olaparib)
over1year
M6620 (VX-970) in Selected Solid Tumors (clinicaltrials.gov)
P2, N=30, Active, not recruiting, Massachusetts General Hospital | N=223 --> 30
Enrollment change
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCC (FA Complementation Group C)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • ARID1A mutation • MYC amplification • CDK12 mutation • CCNE1 amplification • ATRX mutation • FBXW7 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation
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berzosertib (M6620)
over1year
Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
P2, N=50, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial primary completion date: Mar 2021 --> Aug 2021
Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
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Lynparza (olaparib)
over1year
Mutations in DNA Repair Genes and Clinical Outcomes of Patients With Metastatic Colorectal Cancer Receiving Oxaliplatin or Irinotecan-containing Regimens. (PubMed, Am J Clin Oncol)
Mutations in DDR genes were present in 22% of patients with mCRC. In patients with DDR-mutated tumors, initial treatment with FOLFOX/XELOX correlated with improved OS and a numerically higher RR compared with FOLFIRI.
Clinical • Clinical data • Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • RAD51 mutation • CHEK1 expression
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oxaliplatin • irinotecan
over1year
SUKSES-B: Olaparib Monotherapy in Relapsed Small Cell Lung Cancer Patients With HR Pathway Gene Mutations Not Limited to BRCA 1/2 Mutations, ATM Deficiency or MRE11A Mutations (clinicaltrials.gov)
P2, N=15, Completed, Samsung Medical Center | Recruiting --> Completed | N=28 --> 15 | Trial completion date: Sep 2021 --> Jan 2021 | Trial primary completion date: Sep 2021 --> Jan 2021
Clinical • Trial completion • Enrollment change • Trial completion date • Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD54L (DNA Repair And Recombination Protein RAD54) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • WRN (WRN RecQ Like Helicase) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
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BRCA2 mutation • BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • MRE11A mutation • RAD54L mutation • BLM mutation • NBN mutation • WRN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation • RPA1 mutation
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Lynparza (olaparib)
over1year
M6620 (VX-970) in Selected Solid Tumors (clinicaltrials.gov)
P2, N=223, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting
Enrollment closed
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • ARID1A mutation • MYC amplification • CDK12 mutation • CCNE1 amplification • ATRX mutation • FBXW7 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation
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berzosertib (M6620)
over1year
Non-BRCA DNA Damage Repair Gene Alterations and Response to the PARP Inhibitor Rucaparib in Metastatic Castration-Resistant Prostate Cancer: analysis from the phase 2 TRITON2 study. (PubMed, Clin Cancer Res)
Responses were observed in patients with alterations in the DDR genes PALB2, FANCA, BRIP1, and RAD51B. In this prospective, genomics-driven study of rucaparib in mCRPC, we found limited radiographic/PSA responses to PARP inhibition in men with alterations in ATM, CDK12, or CHEK2 However, patients with alterations in other DDR-associated genes (eg, PALB2) may benefit from PARP inhibition.
P2 data • Journal • BRCA Biomarker • PARP Biomarker
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ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRCA (Breast cancer early onset)
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PALB2 mutation • BRIP1 mutation • FANCA mutation • RAD51B mutation
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Rubraca (rucaparib)
almost2years
A Comprehensive Analysis of Alterations in DNA Damage Repair Pathways Reveals a Potential Way to Enhance the Radio-Sensitivity of Esophageal Squamous Cell Cancer. (PubMed, Front Oncol)
Besides, we firstly demonstrated that combination of mirin and NU7441, two inhibitors for HR and NHEJ respectively, with ionizing radiation treatment significantly enhanced DSBs, reduced clonogenic cell survival, inhibited cell proliferation, and promoted cell apoptosis in ESCC cells with DSB pathway gene amplification. These findings suggest that DSB repair pathways were significantly altered in ESCC and inhibiting DSB repair pathways might enhance the radio-sensitivity of ESCC with DSB repair up-regulation.
Journal
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RAD51B (RAD51 Paralog B)
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RAD51B mutation
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NU7441
almost2years
RAD51-Mediated DNA Homologous Recombination Is Independent of PTEN Mutational Status. (PubMed, Cancers (Basel))
Our findings demonstrate definitively that PTEN loss does not alter the RAD51 expression, its paralogs, or the HR activity. Furthermore, deficiency in PTEN alone is not sufficient to impart enhanced sensitivity to PARPi associated with HRD. This study is the first to unequivocally demonstrate that PTEN deficiency is not linked to the RAD51 expression or the HR activity amongst primary neural and non-neural Pten-null cells, PTEN-deficient tumor cell lines, and primary PTEN-mutant GBM patient-derived tissue specimens and BTICs.
Journal • BRCA Biomarker • PARP Biomarker
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PTEN (Phosphatase and tensin homolog) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • RAD51D (RAD51 paralog D)
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PTEN mutation • PTEN expression • RAD51C mutation • RAD51D mutation • RAD51B mutation • BRCA mutation • RAD51 mutation • PTEN loss
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Lynparza (olaparib)
almost2years
Analysis of 11 candidate genes in 849 adult patients with suspected hereditary cancer predisposition. (PubMed, Genes Chromosomes Cancer)
No mutation was identified in RAD51, MRE11A, FAM175A, XRCC2, or MLH3. The involvement of these genes in the hereditary predisposition to cancer cannot be ruled out, although if it exists it is rare or does not seem to involve truncating variants.
Clinical • Journal
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RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD50 (RAD50 Double Strand Break Repair Protein) • MRE11A (MRE11 homolog, double strand break repair nuclease) • BARD1 (BRCA1 Associated RING Domain 1) • FANCM (FA Complementation Group M) • PMS1 (PMS1 protein homolog 1)
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RAD50 mutation • RAD51B mutation • BARD1 mutation • MRE11A mutation • MLH3 mutation • FANCM mutation • RAD51 mutation
almost2years
Clinical • New P1/2 trial • Combination therapy • PARP Biomarker • PD(L)-1 Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • MSH6 (MutS homolog 6) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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HER-2 positive • BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • CHEK2 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
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Keytruda (pembrolizumab) • Lynparza (olaparib) • paclitaxel
2years
Kaposi Sarcoma in Association With an Extracavitary Primary Effusion Lymphoma Showing Unusual Intravascular Involvement: Report of a Case Harboring a FAM175A Germline Mutation. (PubMed, Am J Dermatopathol)
The diagnosis of PEL, solid variant, was made. Next-generation sequencing analysis of the tumorous and normal tissue detected a pathogenic germline mutation of the FAM175A gene and somatic mutations in BRCA2 and RAD51B (in both sarcoma and lymphoma specimens), and INPP4B and RICTOR (in lymphoma specimen only).
Clinical • Journal • BRCA Biomarker
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BRCA2 (Breast cancer 2, early onset) • CD38 (CD38 Molecule) • RAD51B (RAD51 Paralog B) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2)
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BRCA2 mutation • RAD51B mutation
2years
EVOLVE: A Multicenter Open-Label Single-Arm Clinical and Translational Phase II Trial of Cediranib Plus Olaparib for Ovarian Cancer after PARP Inhibition Progression. (PubMed, Clin Cancer Res)
This is currently the largest post-PARPi study identifying genomic mechanisms of resistance to PARPis. In this setting, the activity of cediranib-olaparib varied according to the PARPi resistance mechanism.
Clinical • P2 data • Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CCNE1 (Cyclin E1) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • RAD51B (RAD51 Paralog B) • SLFN11 (Schlafen Family Member 11)
|
BRCA2 mutation • BRCA1 mutation • CCNE1 amplification • RAD51B mutation
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Lynparza (olaparib) • Recentin (cediranib)
over2years
[VIRTUAL] Molecular profiling of neuroendocrine tumors (ESMO-GI 2020)
Legal entity responsible for the study The authors. Funding Has not received any funding.
BRCA Biomarker
|
BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MSH2 (MutS Homolog 2) • CDH1 (Cadherin 1) • RAD51B (RAD51 Paralog B) • CHEK2 (Checkpoint kinase 2)
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BRCA2 mutation • PALB2 mutation • CHEK2 mutation • MSH2 mutation • RAD51B mutation • MLH3 mutation
over2years
[VIRTUAL] Exploring impact of mutations in non-BRCA DNA damage response (DDR) and non-DDR genes on efficacy in phase III EMBRACA study of talazoparib (TALA) in patients (pts) with germline BRCA1/2 mutated (gBRCAm) HER2-negative (HER2-) advanced breast cancer (ABC). (ASCO 2020)
Selection based on gBRCA mutational status is appropriate to identify HER2─ ABC pts with potential for clinical benefit from TALA, with the total number of tumor mutations in BRCA1/2 and other DDR genes not impacting response (within the gBRCAm subset). TP53 mutations were associated with shorter PFS, likely reflecting the worse outcomes observed in gBRCA1m patients. Additional correlative analyses are ongoing.
Clinical • P3 data • BRCA Biomarker • PARP Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • ATR (Ataxia telangiectasia and Rad3-related protein) • BRCA (Breast cancer early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • STAG2 (Stromal Antigen 2) • BARD1 (BRCA1 Associated RING Domain 1) • FANCG (FA Complementation Group G)
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TP53 mutation • BRCA2 mutation • BRCA1 mutation • PIK3CA mutation • HER-2 negative • PALB2 mutation • CDK12 mutation • BRIP1 mutation • FANCA mutation • STAG2 mutation • RAD51B mutation • BARD1 mutation • NBN mutation • FANCG mutation
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FoundationOne® CDx
|
Talzenna (talazoparib)
over2years
ORZORA: To Assess the Efficacy and Safety of Olaparib Maintenance Monotherapy in the Treatment of Ovarian Cancer (clinicaltrials.gov)
P4, N=178, Active, not recruiting, AstraZeneca | Trial completion date: Nov 2019 --> Jun 2021
Clinical • Trial completion date • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • BRCA (Breast cancer early onset) • MUC16 (Mucin 16, Cell Surface Associated) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA2 mutation • BRCA1 mutation • CHEK2 mutation • RAD51B mutation • BARD1 mutation • BRCA mutation
|
Lynparza (olaparib)
over2years
NEO: A Study of Olaparib Prior to Surgery and Chemotherapy in Ovarian, Primary Peritoneal, and Fallopian Tube Cancer (clinicaltrials.gov)
P2, N=71, Recruiting, University Health Network, Toronto | Trial completion date: Jun 2020 --> Dec 2021 | Trial primary completion date: Dec 2019 --> Jun 2021
Clinical • Trial completion date • Trial primary completion date • BRCA Biomarker • PARP Biomarker
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • RAD51D (RAD51 paralog D) • MUC16 (Mucin 16, Cell Surface Associated) • BARD1 (BRCA1 Associated RING Domain 1) • FANCM (FA Complementation Group M) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D)
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BRCA2 mutation • BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • FANCM mutation • MUC16 expression • PPM1D mutation • RAD51 mutation
|
Lynparza (olaparib)