^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    GENE:

    RAD54L (DNA Repair And Recombination Protein RAD54)

    i
    Other names: RAD54L, DNA Repair And Recombination Protein RAD54, RAD54 Homolog, RAD54A, HRAD54, HHR54, RAD54 Like (S. Cerevisiae), RAD54 (S.Cerevisiae)-Like
    6d
    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)
    9d
    Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations (clinicaltrials.gov)
    P2, N=36, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • BACH1 (BTB Domain And CNC Homolog 1) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation
    |
    Talzenna (talazoparib)
    12d
    A phase II study evaluating safety and efficacy of niraparib in patients with previously treated homologous recombination defective metastatic esophageal/gastroesophageal junction/proximal gastric adenocarcinoma. (PubMed, Front Oncol)
    The most common adverse events seen were anemia, fatigue, and thrombocytopenia. In patients with metastatic EAC, single agent niraparib as second line therapy is not an effective option.
    P2 data • Journal • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • PARP2 (Poly(ADP-Ribose) Polymerase 2)
    |
    FANCA deletion
    |
    Zejula (niraparib)
    26d
    Repeat expansion in a Fragile X model is independent of double strand break repair mediated by Pol θ, Rad52, Rad54l or Rad54b. (PubMed, bioRxiv)
    These observations put major constraints on what pathways are likely to drive expansion. Together with our previous demonstration of the protective effect of nucleases like EXO1 and FAN1, and the importance of Pol β, they suggest a plausible model for late steps in the expansion process.
    Journal
    |
    MSI (Microsatellite instability) • RAD54L (DNA Repair And Recombination Protein RAD54) • RAD52 (RAD52 Homolog DNA Repair Protein) • RAD54B (RAD54 Homolog B)
    |
    RAD54L mutation • RAD52 mutation
    3ms
    KNTC1 functions as a potential biomarker and oncogene regulating proliferation, migration and apoptosis in gastric cancer. (PubMed, Int Immunopharmacol)
    KNTC1 acts as a potential diagnostic and prognostic marker for GC. It may promote proliferation and migration while inhibiting apoptosis of GC cells via the PI3K/Akt/mTOR pathway.
    Journal
    |
    TACC3 (Transforming acidic coiled-coil containing protein 3) • RAD54L (DNA Repair And Recombination Protein RAD54)
    3ms
    Homologous recombination deficiency gene panel analysis results in synchronous endometrial and ovarian cancers. (PubMed, Rev Assoc Med Bras (1992))
    Pathogenic variations confirming the diagnosis of synchronous endometrial ovarian cancer with genetic alterations were identified in all but one case. ATM gene mutation emerged as the most common alteration and has a potential association with a favorable prognosis.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54)
    |
    TP53 mutation • HRD • RAD51D mutation • BARD1 mutation • RAD54L mutation • TP53 mutation + ATM mutation
    3ms
    Disparate requirements for RAD54L in replication fork reversal. (PubMed, Nucleic Acids Res)
    Conversely, in the FBH1 pathway, branch migration activity of RAD54L is essential, and FBH1 engagement is dependent on its concerted action with RAD54L. Collectively, our results reveal disparate requirements for RAD54L in two distinct RAD51-mediated fork reversal pathways, positing its potential as a future therapeutic target.
    Journal
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • RAD54L (DNA Repair And Recombination Protein RAD54) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
    3ms
    BRACeD: Carboplatin or Olaparib for BRcA Deficient Prostate Cancer (clinicaltrials.gov)
    P2, N=100, Recruiting, VA Office of Research and Development | Trial primary completion date: Aug 2024 --> Aug 2025
    Trial primary completion date
    |
    RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • RAD54L (DNA Repair And Recombination Protein RAD54)
    |
    ATRX mutation • RAD54L mutation • RAD51 mutation
    |
    Lynparza (olaparib) • carboplatin
    3ms
    PARPi-PANC: Niraparib As First Line Therapy with Metastatic Homologous Repair-deficient Pancreatic Cancer (clinicaltrials.gov)
    P2, N=0, Withdrawn, Centre Leon Berard | N=28 --> 0 | Recruiting --> Withdrawn
    Enrollment change • Trial withdrawal • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCD2 (FA Complementation Group D2)
    |
    HRD signature
    |
    Zejula (niraparib)
    3ms
    Circulating Tumor DNA (ctDNA) Monitoring in the Assessment and Prediction of the Efficacy of PARP Inhibitors (PARPi) (clinicaltrials.gov)
    P=N/A, N=30, Recruiting, Sun Yat-sen University | Trial completion date: Aug 2023 --> Aug 2025
    Trial completion date • Circulating tumor DNA
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • BRCA1 mutation + ATM mutation • CHEK1 expression
    4ms
    Targeting proliferating cell nuclear antigen enhances ionizing radiation-induced cytotoxicity in prostate cancer cells. (PubMed, Prostate)
    These data provide a strong rationale for the therapy studies using PCNA-I1S or R9-AR-PIP in combination with X-ray radiation against CRPC tumors in preclinical models.
    Journal • PARP Biomarker
    |
    HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • CCNA2 (Cyclin A2) • XRCC2 (X-Ray Repair Cross Complementing 2) • PCNA (Proliferating cell nuclear antigen) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) • EXO1 (Exonuclease 1)
    |
    Xtandi (enzalutamide)
    4ms
    Genomic landscape of early-stage prostate adenocarcinoma in Mexican patients: an exploratory study. (PubMed, Discov Oncol)
    This pilot study reveals the mutational landscape of early-stage prostate adenocarcinoma in Mexican men, providing a first approach to understand the mutational patterns and actionable mutations in early prostate cancer can inform personalized treatment approaches and reduce the underrepresentation in genomic cancer studies.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA (Breast cancer early onset) • FAT1 (FAT atypical cadherin 1) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • RAD54L (DNA Repair And Recombination Protein RAD54) • ARAF (A-Raf Proto-Oncogene) • CSMD3 (CUB And Sushi Multiple Domains 3) • SNCA (Synuclein Alpha)
    5ms
    A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors (clinicaltrials.gov)
    P1/2, N=120, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting | N=13 --> 120
    Enrollment open • Enrollment change
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)
    5ms
    Identification of Key Genes Associated with Polycystic Ovarian Syndrome and Endometrial and Ovarian Cancer through Bioinformatics. (PubMed, J Hum Reprod Sci)
    Potential drugs for PCOS and EC include quercetin, calcitriol and testosterone; for PCOS and OC, eugenol and 1-chloro-2,4-dinitrobenzene are identified. These findings offer insights into potential therapeutic targets and pathways linking PCOS with EC and OC, enhancing our understanding of the molecular mechanisms involved in these associations.
    Journal
    |
    PRDX1 (Peroxiredoxin 1) • GSTP1 (Glutathione S-transferase pi 1) • PLK1 (Polo Like Kinase 1) • HMOX1 (Heme Oxygenase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • NQO1 (NAD(P)H dehydrogenase, quinone 1) • BOP1 (BOP1 Ribosomal Biogenesis Factor) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1) • RECQL4( RecQ Like Helicase 4) • CDT1 (Chromatin Licensing And DNA Replication Factor 1)
    6ms
    Case report: Remarkable response to later-line surufatinib in an adult patient with liver metastatic of pancreatoblastoma. (PubMed, Front Pharmacol)
    Surufatinib has demonstrated a progression-free survival (PFS) of no less than 14 months, and the patient's survival has endured for a duration of 33 months. This indicates the potential efficacy of surufatinib as a viable therapeutic alternative for adult patients afflicted with PB.
    Journal • Metastases
    |
    TMB (Tumor Mutational Burden) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • KRT19 (Keratin 19)
    |
    Aidixi (disitamab vedotin) • Sulanda (surufatinib)
    7ms
    A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors (clinicaltrials.gov)
    P1/2, N=13, Suspended, National Cancer Institute (NCI) | N=120 --> 13 | Recruiting --> Suspended
    Enrollment change • Trial suspension
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)
    7ms
    A Study Evaluating Safety and Efficacy of Niraparib in Patients With Previously Treated Metastatic Esophageal/Gastroesophageal Junction/Proximal Gastric Adenocarcinoma (clinicaltrials.gov)
    P2, N=14, Terminated, Shadia Jalal, MD | N=43 --> 14 | Active, not recruiting --> Terminated; Due to slow accruals
    Enrollment change • Trial termination • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
    |
    Zejula (niraparib)
    7ms
    A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors (clinicaltrials.gov)
    P1/2, N=120, Recruiting, National Cancer Institute (NCI) | N=85 --> 120
    Enrollment change
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)
    7ms
    Modification Effects of Homologous Recombination Repair Gene Polymorphisms on the Associations Between Urinary Metals and Breast Cancer Risk. (PubMed, Biol Trace Elem Res)
    This study showed compelling evidence for the interaction between genetic variants within the HRR system and urinary metals on BC risk. Our findings highlight the need to consider genetic makeup when evaluating the carcinogenic or protective potential of metals.
    Journal
    |
    HRD (Homologous Recombination Deficiency) • RAD54L (DNA Repair And Recombination Protein RAD54) • LIG3 (DNA Ligase 3)
    8ms
    KNIGHTS: High-Risk Metachronous Oligometastatic Prostate Cancer Trial (clinicaltrials.gov)
    P2, N=88, Recruiting, University of Maryland, Baltimore | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • RAD54L (DNA Repair And Recombination Protein RAD54)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • FANCA mutation
    |
    Zejula (niraparib) • abiraterone acetate • prednisone
    8ms
    Characterization of a G2M checkpoint-related gene model and subtypes associated with immunotherapy response for clear cell renal cell carcinoma. (PubMed, Heliyon)
    Two clusters of ccRCC were identified using the "ConsensusClusterPlus" package, cluster 1 exhibited a worse survival rate and was resistant to chemotherapeutic drugs of Axitinib, Erlotinib, Pazopanib, Sunitinib, and Temsirolimus, but not Sorafenib. In conclusion, our study offers valuable insights into the molecular mechanisms underlying ccRCC, identifying potential prognostic genes and molecular subtypes associated with the G2M checkpoint. These findings hold promise for guiding personalized treatment strategies in the management of ccRCC.
    Journal • IO biomarker
    |
    RAD54L (DNA Repair And Recombination Protein RAD54) • E2F2 (E2F Transcription Factor 2) • UBE2C (Ubiquitin Conjugating Enzyme E2 C) • GTSE1 (G2 And S-Phase Expressed 1)
    |
    erlotinib • sorafenib • sunitinib • pazopanib • Torisel (temsirolimus) • Inlyta (axitinib)
    9ms
    BrUOG 360: A Study of Copanlisib Combined With Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=13, Active, not recruiting, Brown University | Trial completion date: May 2024 --> Jan 2027 | Trial primary completion date: Jan 2024 --> Jan 2027
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    BRIP1 mutation
    |
    Rubraca (rucaparib) • Aliqopa (copanlisib)
    9ms
    NIRADO: Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (clinicaltrials.gov)
    P2, N=51, Suspended, Gustave Roussy, Cancer Campus, Grand Paris | N=112 --> 51 | Trial completion date: Mar 2027 --> Dec 2027 | Recruiting --> Suspended | Trial primary completion date: Mar 2024 --> Dec 2024
    Enrollment change • Trial completion date • Trial suspension • Trial primary completion date • Pan tumor
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • ARID2 (AT-Rich Interaction Domain 2) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)
    |
    HER-2 positive • HER-2 amplification • DDR • PBRM1 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • NBN mutation • DRD
    |
    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    9ms
    ARIANES: Efficacy and Safety of the Combination of Rucaparib (PARP Inhibitor) and Atezolizumab (Anti-PD-L1 Antibody) in Patients With DNA Repair-deficient or Platinum-sensitive Solid Tumors (clinicaltrials.gov)
    P2, N=130, Suspended, Gustave Roussy, Cancer Campus, Grand Paris | N=1000 --> 130 | Trial primary completion date: Apr 2024 --> Dec 2024
    Enrollment change • Trial primary completion date • Pan tumor
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • IL2 (Interleukin 2) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)
    |
    DDR • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • NBN mutation • DRD
    |
    Tecentriq (atezolizumab) • Rubraca (rucaparib)
    10ms
    ORCHID: Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations (clinicaltrials.gov)
    P2, N=20, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Mar 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression
    |
    Lynparza (olaparib)
    10ms
    RNA m5C modification upregulates E2F1 expression in a manner dependent on YBX1 phase separation and promotes tumor progression in ovarian cancer. (PubMed, Exp Mol Med)
    Moreover, E2F1 transcriptionally regulates the expression of the oncogenes MYBL2 and RAD54L, driving ovarian cancer progression. Thus, our study delineates a NSUN2-E2F1-NSUN2 loop regulated by m5C modification in a manner dependent on YBX1 phase separation, and this previously unidentified pathway could be a promising target for ovarian cancer treatment.
    Journal
    |
    RAD54L (DNA Repair And Recombination Protein RAD54) • YBX1 (Y-Box Binding Protein 1) • MYBL2 (MYB Proto-Oncogene Like 2) • E2F1 (E2F transcription factor 1) • NSUN2 (NOP2/Sun RNA Methyltransferase 2)
    10ms
    Treatment patterns and outcomes in metastatic castration-resistant prostate cancer patients with and without somatic or germline alterations in homologous recombination repair genes. (PubMed, Ann Oncol)
    Worse outcomes were observed for mCRPC patients in the BRCA subgroup compared with non-BRCA subgroups, either HRR non-BRCA or non-HRR. Despite its heterogeneity, the HRR non-BRCA subgroup presented worse outcomes than the non-HRR subgroup. Screening early for HRR mutations, especially BRCA1/2, is crucial in improving mCRPC patient prognosis.
    Journal • BRCA Biomarker • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • HDAC2 (Histone deacetylase 2)
    |
    BRCA2 mutation • BRCA1 mutation
    10ms
    A Study Evaluating Safety and Efficacy of Niraparib in Patients With Previously Treated Metastatic Esophageal/Gastroesophageal Junction/Proximal Gastric Adenocarcinoma (clinicaltrials.gov)
    P2, N=43, Active, not recruiting, Shadia Jalal, MD | Trial completion date: Nov 2024 --> Jul 2024 | Trial primary completion date: Nov 2023 --> Feb 2023
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • NBN mutation
    |
    Zejula (niraparib)
    10ms
    Pembrolizumab, Olaparib, and Temozolomide for People With Glioma (clinicaltrials.gov)
    P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FGFR (Fibroblast Growth Factor Receptor) • CDK12 (Cyclin dependent kinase 12) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    CDKN2A deletion • BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide
    11ms
    KNIGHTS: High-Risk Metachronous Oligometastatic Prostate Cancer Trial (clinicaltrials.gov)
    P2, N=88, Not yet recruiting, University of Maryland, Baltimore
    New P2 trial • Metastases
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • RAD54L (DNA Repair And Recombination Protein RAD54)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • FANCA mutation
    |
    Zejula (niraparib) • abiraterone acetate
    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)
    12ms
    Pembrolizumab, Olaparib, and Temozolomide for People With Glioma (clinicaltrials.gov)
    P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FGFR (Fibroblast Growth Factor Receptor) • CDK12 (Cyclin dependent kinase 12) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    CDKN2A deletion • BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide
    12ms
    DIDO: Niraparib and Dostarlimab in HRD Solid Tumors (clinicaltrials.gov)
    P2, N=30, Recruiting, West Cancer Center | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCI (FA Complementation Group I)
    |
    BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • FANCI mutation • RAD51 mutation
    |
    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    1year
    Acute irradiation induces a senescence-like chromatin structure in mammalian oocytes. (PubMed, Commun Biol)
    Notably, analysis of biological aging using an oocyte-specific RNA clock revealed cellular communication, posttranslational protein modifications, chromatin and histone dynamics as the top cellular processes that are dysregulated in both senescent and irradiated oocytes. Our results indicate that unfolding of heterochromatin fibers following acute genotoxic stress or cellular aging induced the formation of distended satellites and that abnormal chromatin structure together with increased chromocenter mobility leads to chromosome instability in senescent oocytes.
    Journal
    |
    RAD54L (DNA Repair And Recombination Protein RAD54) • FERMT1 (Fermitin Family Member 1)
    1year
    Real-world homologous recombination repair mutation (HRRm) testing patterns in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with olaparib in the United States. (ASCO-GU 2024)
    Pts with confirmed mCRPC diagnosis, age ≥21 years, treated with olaparib monotherapy after exposure to abiraterone or enzalutamide, and with positive HRRm status were included. This real-world analysis highlights the need for earlier HRRm testing in pts with mCRPC to allow for optimal timing of novel treatment options that have shown efficacy in a biomarker-selected population. Most pts in this study were tested and diagnosed with HRRm many months after mCRPC diagnosis, at which point they had high levels of bone metastasis, multiple sites of distant metastases, and opioid use at the initiation of olaparib treatment. HRR testing in pts before or at the time of mCRPC would allow for olaparib therapy earlier in the disease course.
    Real-world evidence • Clinical • PARP Biomarker • BRCA Biomarker • Real-world • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    BRCA1 mutation • ATM mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
    |
    Lynparza (olaparib) • Xtandi (enzalutamide) • abiraterone acetate
    1year
    Real-world effectiveness of PARP inhibitors (PARPi) in metastatic castration-resistant prostate cancer (mCRPC) by genomic homologous recombination repair (HRR) alterations and homologous recombination deficiency signature (HRDsig). (ASCO-GU 2024)
    We observe no significant outcomes difference between non-BRCAalt groups (defined as ATM, other HRR, and no HRR) in this cohort with respect to proxies of drug effectiveness. These results are largely consistent with biomarker-defined subgroup analyses from completed clinical trials. However, HRDsig may be able to identify a small non-BRCAalt subgroup with enhanced benefit.
    Clinical • Real-world evidence • BRCA Biomarker • PARP Biomarker • Real-world effectiveness • Real-world • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    BRCA2 mutation • HRD • HRD signature
    1year
    Efficacy of olaparib (O) plus abiraterone (A) versus placebo (P) plus A in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with single homologous recombination repair gene mutations (HRRm) in the PROpel trial. (ASCO-GU 2024)
    BRCA2, ATM and CDK12 were the most prevalent single gene mutations and clinical benefit was observed with O + A. Other single gene mutations were rare, limiting interpretation. The greatest treatment benefit was observed in pts with BRCA mutations. Clinical trial information: NCT03732820.NR, not reached; BRIP1, RAD51B, RAD51D n=1; CHEK1, RAD51C n=0.
    Clinical • PARP Biomarker • BRCA Biomarker • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    ATM mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BRCA mutation • CHEK1 mutation • BRCA2 mutation + ATM mutation • CHEK1 expression
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    |
    Lynparza (olaparib) • abiraterone acetate
    1year
    Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations (clinicaltrials.gov)
    P2, N=36, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • BACH1 (BTB Domain And CNC Homolog 1) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation
    |
    Talzenna (talazoparib)
    1year
    Multi-Level Control of Myeloma Cell Proliferation and Genomic Instability By the PDZ Binding Kinase (PBK) (ASH 2023)
    Surprisingly, we observed that PBK also directly phosphorylates DNA repair/HR genes, such as flap structure-specific nuclease 1 (FEN1), and that PBK inhibition reduces spontaneous and chemotherapy (melphalan)-induced genomic instability ( P < 0...In summary, we demonstrate that PBK drives DNA replication and genomic instability in MM cells by acting at multiple levels. Therefore, PBK inhibitors investigated here have the potential to impair growth and increase the efficacy of chemotherapeutic agents while reducing spontaneous as well as chemotherapeutic agent-induced genomic instability in MM.
    BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • RAD54L (DNA Repair And Recombination Protein RAD54) • FOXM1 (Forkhead Box M1) • PBK (PDZ Binding Kinase) • CENPA (Centromere protein A) • FEN1 (Flap Structure-Specific Endonuclease 1) • MAD2L1 (Mitotic Arrest Deficient 2 Like 1) • RAD54B (RAD54 Homolog B)
    |
    melphalan
    1year
    Development and introduction of methods for risk assessment and diagnosis of hereditary breast cancer in Armenia (ABC 2023)
    A hi-gh percentage of mutations in the sample indicates the relevance of this study. A unified database of frequencies of hereditary mutations in the genes of the DNA repair system for the population of Armenia will allow to assess the risks of hereditary breast cancer in Armenia, draw conclusions and develop appropriate recommendations.
    BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • EPCAM (Epithelial cell adhesion molecule) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    TP53 mutation • BRCA2 mutation • BRCA1 mutation • ATM mutation • CDH1 mutation
    1year
    Exploiting TLK1 and Cisplatin Synergy for Synthetic Lethality in Androgen-Insensitive Prostate Cancer. (PubMed, Biomedicines)
    By elucidating the role of TLK1 in CPT resistance, this study provides valuable insights into potential therapeutic targets to overcome PCa resistance to CPT chemotherapy. Further investigations into TLK1 inhibition in combination with other DNA-damaging agents may pave the way for more effective and targeted treatments for PCa and other cancers that exhibit resistance to traditional chemotherapy agents.
    Journal • Synthetic lethality
    |
    HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • RAD54L (DNA Repair And Recombination Protein RAD54) • RAD54B (RAD54 Homolog B) • TLK1 (Tousled Like Kinase 1)
    |
    cisplatin
    1year
    Trial of Olaparib in Patients With Metastatic Urothelial Cancer Harboring DNA Damage Response Gene Alterations (clinicaltrials.gov)
    P2, N=19, Completed, Matthew Galsky | Active, not recruiting --> Completed | N=30 --> 19
    Trial completion • Enrollment change • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • POLE (DNA Polymerase Epsilon) • ERCC2 (Excision repair cross-complementation group 2) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • ERCC5 (ERCC Excision Repair 5 Endonuclease 2) • FANCF (FA complementation group F) • WRN (WRN RecQ Like Helicase) • XRCC2 (X-Ray Repair Cross Complementing 2) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • RAD52 (RAD52 Homolog DNA Repair Protein) • ERCC3 (ERCC Excision Repair 3, TFIIH Core Complex Helicase Subunit) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • RECQL4( RecQ Like Helicase 4) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C) • XRCC3 (X-Ray Repair Cross Complementing 3)
    |
    Lynparza (olaparib)