News - RAD52 mutation

2ms

Identification of different classes of genome instability suppressor genes through analysis of DNA damage response markers. (PubMed, G3 (Bethesda))

DDS + DGIS- genes, including many transcription-related genes, likely suppress damage that is normally repaired properly or prevent inappropriate signaling, whereas DDS- DGIS + genes, like PIF1, do not suppress damage but likely promote its proper, non-mutagenic repair. Thus, induction of DNA damage markers is not a reliable indicator of increased genome instability, and the DDS and DGIS categories define of mechanistically distinct groups of genes.

2 months ago

Journal

|

RAD52 (RAD52 Homolog DNA Repair Protein)

|

RAD52 mutation

4ms

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

4 months ago

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)

11ms

Identification of small molecule inhibitors of RAD52 for breast cancer therapy: in silico approach. (PubMed, J Biomol Struct Dyn)

Furthermore, a drug-like properties of lead molecules (8758 and 10593) were also seen via ADMET analysis. Based on our computational analysis, we hypothesize that a small molecule 8758 and 10593 possess the therapeutic potential in the management for breast cancer patients with a BRCA mutation via targeting RAD52.Communicated by Ramaswamy H. Sarma.

11 months ago

Journal • BRCA Biomarker

|

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • RAD52 (RAD52 Homolog DNA Repair Protein)

|

BRCA mutation • RAD52 mutation

over1year

SUKSES-B2: Olaparib and Bevacizumab in Relapsed Small Cell Lung Cancer Subjects (clinicaltrials.gov)

P2, N=28, Recruiting, Se-Hoon Lee | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Jun 2023

over 1 year ago

Trial completion date • 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)

over1year

A moving target for drug discovery: Structure activity relationship and many genome (de)stabilizing functions of the RAD52 protein. (PubMed, DNA Repair (Amst))

Yet, the effective pharmacological inhibitors of RAD52 have not been forthcoming. In this review, we discuss advances in the state of our knowledge of the RAD52 structure, activities and cellular functions, with a specific focus on the features that make RAD52 an attractive, but difficult drug target.

over 1 year ago

Journal • BRCA Biomarker • PARP Biomarker

|

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • RAD52 (RAD52 Homolog DNA Repair Protein)

|

RAD52 mutation

over1year

Pan-cancer analysis of co-occurring mutations in RAD52 and the BRCA1-BRCA2-PALB2 axis in human cancers. (PubMed, PLoS One)

Molecular modeling also revealed that pathogenic RAD52 mutations co-occurring with mutations in BRCA2-BRCA1-PALB2 axis are either expected to attenuate its SSA function or its interaction with DNA. This study extends previous breast cancer findings to other cancer types and shows that co-occurring mutations likely destabilize HR by similar mechanisms as in breast cancers.

over 1 year ago

Journal • BRCA Biomarker • Pan tumor

|

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51 (RAD51 Homolog A) • RAD52 (RAD52 Homolog DNA Repair Protein)

|

BRCA1 mutation • PALB2 mutation • RAD52 mutation

over2years

[VIRTUAL] A Targeted Next-Generation Sequencing Assay to Characterize Homologous Recombination Deficiency (HRD) Reveals Associations between Homologous Recombination Repair Genes and Genomic Instability (AMP 2021)

HRD is an emerging biomarker for sensitivity to cisplatin and for inhibitors of poly (ADPribose) polymerase (PARP)... We developed a comprehensive genomic profiling assay that determines genomic %LOH to characterize HRD. We established that tumor samples with BRCA1/2 alterations exhibit significantly higher %LOH relative to samples without HRR alterations. Further, samples with biallelic BRCA1/2 mutations have higher %LOH relative to monoallelic mutations.

over 2 years ago

PARP Biomarker • BRCA Biomarker • Next-generation sequencing

|

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD52 (RAD52 Homolog DNA Repair Protein)

|

BRCA2 mutation • BRCA1 mutation • HRD • BRIP1 mutation • RAD52 mutation

|

Oncomine™ Comprehensive Assay Plus

|

cisplatin

over2years

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

over 2 years ago

Clinical • Enrollment open • 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) • 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)

almost3years

SUKSES-B2: Olaparib and Bevacizumab in Relapsed Small Cell Lung Cancer Subjects (clinicaltrials.gov)

P2, N=28, Not yet recruiting, Keunchil Park

almost 3 years ago

Clinical • New P2 trial • 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) • 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)

almost3years

Identification of a novel heterozygous germline RAD52 missense mutation in a patient with gallbladder carcinoma: A case report. (PubMed, Medicine (Baltimore))

We identified a novel heterozygous germline RAD52 missense mutation in a patient with gallbladder carcinoma. Our results added to the current body of knowledge. It also provides new insights into genetic counseling and targeted therapeutic strategies for patients with gallbladder carcinoma.

almost 3 years ago

Clinical • Journal

|

RAD52 (RAD52 Homolog DNA Repair Protein)

|

RAD52 mutation

3years

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

3 years ago

Clinical • Trial completion • Enrollment change • Trial completion date • Trial primary completion date

|

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) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • WRN (WRN RecQ Like Helicase) • 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 • MRE11A mutation • RAD54L mutation • NBN mutation • WRN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation • RPA1 mutation

|

Lynparza (olaparib)

over3years

RAD52 S346X Variant Reduces Breast Cancer Risk in BRCA2 Mutation Carriers. (PubMed, Mol Oncol)

A noncoding polymorphism at 5´UTR in RAD51 has been shown by multiple independent studies to increase breast cancer risk in BRCA2 carriers (Antoniou et al., 2007). RAD51 is the key protein that interacts with both BRCA1 and BRCA2 and is required for the repair of double strand breaks by homologous recombination (Pellegrini and Venkitaraman, 2004).

over 3 years ago

Journal • BRCA Biomarker

|

BRCA2 (Breast cancer 2, early onset) • RAD52 (RAD52 Homolog DNA Repair Protein)

|

BRCA2 mutation • RAD52 mutation

almost4years

A novel TJP1-ROS1 fusion in malignant peripheral nerve sheath tumor responding to crizotinib: A case report. (PubMed, Medicine (Baltimore))

To our knowledge, this is the first report of the TJP1-ROS1 fusion, which expands the list of gene fusions and highlights new targets for targeted therapy. Also, our case underlines the value of multi-gene panel next-generation sequencing for diagnosis of MPNST.

almost 4 years ago

Clinical • Journal

|

ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MDM2 (E3 ubiquitin protein ligase) • CD34 (CD34 molecule) • SOX9 (SRY-Box Transcription Factor 9) • CD31 (Platelet and endothelial cell adhesion molecule 1) • RAD52 (RAD52 Homolog DNA Repair Protein) • STAT6 (Signal transducer and activator of transcription 6) • GFAP (Glial Fibrillary Acidic Protein)

|

ROS1 fusion • BAP1 mutation • RAD52 mutation

|

Xalkori (crizotinib)

almost4years

Gender differences in molecular-guided therapy recommendations for metastatic malignant mesothelioma. (PubMed, Thorac Cancer)

Our observations suggest that a molecular-guided treatment approach is feasible for the management of advanced malignant mesothelioma. Our analysis revealed gender specific differences in PDGFRα expression that should be further evaluated in clinical trials.

almost 4 years ago

Journal • PD(L)-1 Biomarker

|

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • BAP1 (BRCA1 Associated Protein 1) • FANCA (FA Complementation Group A)

|

TP53 mutation • BAP1 mutation • FANCA mutation • RAD52 mutation

almost4years

[VIRTUAL] Rad52 residues associated with colonic adenocarcinoma dictate its cooperative assembly on ssDNA during homologous recombination (AACR-II 2020)

Finally, we show that this cooperativity in Rad52 selectively affects the DNA binding of RPA-DBD-D on a 5′ overhang DNA substrate. A detailed mechanistic insight into Rad52-ssDNA binding will aid in a better understanding of HR, which can contribute to the development of small-molecule inhibitor drugs that can be used as effective chemotherapeutic agents against cancers in the future.

almost 4 years ago

BRCA Biomarker

|

BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • RAD52 (RAD52 Homolog DNA Repair Protein)

|

BRCA2 mutation • RAD51 mutation • RAD52 mutation

4years

The RAD52-S346X variant reduces risk of developing breast cancer in carriers of pathogenic germline BRCA2 mutations. (PubMed, Mol Oncol)

Altogether, we identified a genetic modifier that protects against breast cancer in women who carry pathogenic mutations in BRCA2 (P = 0.0008), and to a lesser extent BRCA1 (P = 0.02). This RAD52 mutation causes a reduction in DSB repair by SSA, suggesting that defects in RAD52-dependent DSB repair are linked to reduced tumor risk in BRCA2-mutation carriers.

4 years ago

Journal • BRCA Biomarker

|

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)

|

BRCA2 mutation • BRCA1 mutation • RAD52 mutation