News - RAD51 mutation

RAD51 as an immunohistochemistry-based marker of poly(ADP-ribose) polymerase inhibitor resistance in ovarian cancer. (PubMed, Front Oncol)

Analysis of matched pre- and post-PARPi samples collected from 15 patients indicated an increase in the RAD51 H-score upon progression on PARPi, particularly among pre-PARPi low-RAD51-expressing patients. RAD51 is a potential functional IHC biomarker of de novo and acquired PARPi resistance in BRCA-mutated ovarian cancer and can be used to fine-tune ovarian cancer treatment.

7 days ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A)

BRCA mutation • RAD51 mutation

10d

Comprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO (clinicaltrials.gov)

P2, N=11, Active, not recruiting, Institut fuer Frauengesundheit | Recruiting --> Active, not recruiting | N=89 --> 11 | Trial primary completion date: Jan 2024 --> Jan 2025

10 days ago

Enrollment closed • Enrollment change • Trial primary completion date • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • XRCC2 (X-Ray Repair Cross Complementing 2) • FANCC (FA Complementation Group C) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

BRCA2 mutation • BRCA1 mutation • HER-2 amplification • HER-2 negative • HRD • ATM mutation • PALB2 mutation • ER positive + PGR positive • CHEK2 mutation • PGR positive • RAD51C mutation • RAD51D mutation • BARD1 mutation • RAD51 mutation

Keytruda (pembrolizumab) • Lynparza (olaparib)

22d

Endometrial Cancer in a Family With RAD51D Gene Mutation. (PubMed, Int J Gynecol Pathol)

We report a family of French Canadian ancestry with a germline mutation in RAD51D and two sisters presenting with endometrial carcinoma, endometrioid-type. The risk factors for endometrial adenocarcinoma, endometrioid-type are discussed in the context of the RAD51-associated carcinomas described to date.

22 days ago

Journal

HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A) • RAD51D (RAD51 paralog D)

HRD • RAD51D mutation • RAD51 mutation

24d

Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)

P1, N=30, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

24 days ago

Enrollment open

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation

Dual-loss of PBRM1 and RAD51 identifies hyper-sensitive subset patients to immunotherapy in clear cell renal cell carcinoma. (PubMed, Cancer Immunol Immunother)

PBRM1 and RAD51 dual-loss ccRCC indicates superior responses to immunotherapy. Dual-loss ccRCC harbors an immune-desert microenvironment but enriched with M1 macrophages. Dual-loss ccRCC is susceptible to defective homologous recombination but possesses high chromosomal stability.

1 month ago

Journal • IO biomarker

HRD (Homologous Recombination Deficiency) • PBRM1 (Polybromo 1) • RAD51 (RAD51 Homolog A)

HRD • PBRM1 mutation • RAD51 mutation

2ms

CERTIS1: Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies (clinicaltrials.gov)

P1/2, N=490, Recruiting, AstraZeneca | Trial primary completion date: Apr 2025 --> Jan 2026

2 months ago

Trial primary completion date • Combination therapy • Metastases

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) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

BRCA2 mutation • BRCA1 mutation • HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation • RAD51 mutation

temozolomide • Enhertu (fam-trastuzumab deruxtecan-nxki) • datopotamab deruxtecan (DS-1062a) • AZD9574

2ms

Genetically driven predisposition leads to an unusually genomic unstable renal cell carcinoma. (PubMed, Discov Oncol)

While BRCA1 and RAD51 germline mutations are well-characterised in breast and ovarian cancer, their role in renal cell carcinoma is still largely unexplored. The genomic instability detected in this case of renal cell carcinoma, along with the presence of unusual mutations, might offer support to clinicians for the development of patient-tailored therapies.

2 months ago

Journal • Tumor mutational burden • BRCA Biomarker

TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • VHL (von Hippel-Lindau tumor suppressor) • RAD51 (RAD51 Homolog A) • FH (Fumarate Hydratase) • FLCN (Folliculin)

BRCA1 mutation • TMB-H • VHL mutation • MET mutation • FLCN mutation • RAD51 mutation

2ms

A Phase II Study of Rucaparib Monotherapy in Nonmetastatic, Hormone-Sensitive Prostate Cancer Demonstrating "BRCAness" Genotype (ROAR). (PubMed, Oncologist)

Rucaparib demonstrated acceptable toxicity and efficacy signal as an ADT-sparing approach in patients with biochemically recurrent nonmetastatic prostate cancer. It is currently challenging to understand the optimal value of systemic therapy in this disease setting due to the rapidly changing standard of care. Additionally, there are relatively few patients with BRCAness who present with nonmetastatic hormone-sensitive prostate cancer (ClinicalTrials.gov Identifier: NCT03533946).

2 months ago

P2 data • Journal • BRCA Biomarker • PARP 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) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)

ATM mutation • PALB2 mutation • CHEK2 mutation • RAD51 mutation

Rubraca (rucaparib)

2ms

Targeted DNA sequencing of high-grade serous ovarian carcinoma reveals association of TP53 mutations with platinum resistance when combined with gene expression. (PubMed, Int J Cancer)

Targeted DNA sequencing of TP53 combined with transcript quantification may contribute to the concept of precision oncology of HGSC. Future studies should explore targeting the p53 pathway based on specific mutation types and co-analyze the expression and mutational profiles of other key cancer genes.

2 months ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • CSMD1 (CUB And Sushi Multiple Domains 1)

TP53 mutation • BRCA1 mutation • RAD51 mutation

2ms

Multi-omic analysis of serial biopsies to inform biomarkers of sensitivity to olaparib and durvalumab in patients with metastatic BRCA-wildtype triple negative breast cancer (mTNBC) (AACR 2024)

Findings highlight the value of paired Bxs to identify predictive biomarkers of PARPi + immune checkpoint inhibitor sensitivity. The striking predictive value of the BLIA/BLIS signature warrants evaluation in a larger trial. Emerging resistance mechanisms justify AMTEC trial expansion to include PARPi + MEKi or PARPi + AKTi in biomarker selected patients, which is now in progress.

2 months ago

Clinical • Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • BRCA Biomarker • IO biomarker • Metastases • Biopsy • Omic analysis

TMB (Tumor Mutational Burden) • AR (Androgen receptor) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A)

BRCA wild-type • RAD51 mutation

PD-L1 IHC 22C3 pharmDx

Lynparza (olaparib) • Imfinzi (durvalumab)

2ms

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

2 months ago

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)

3ms

Primary fallopian tube cancer followed by primary breast cancer in RAD51C mutation carrier treated with niraparib as first line maintenance therapy: a case report. (PubMed, Hered Cancer Clin Pract)

The patient received three cycles of neoadjuvant chemotherapy with paclitaxel and carboplatin and achieved a complete response. The metachronous breast cancer in this case may be the first report of second primary cancer in fallopian tube cancer patient harboring a RAD51C mutation during niraparib treatment. Further studies are required to determine optimal treatment.

3 months ago

Journal • PARP Biomarker

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • RAD51C (RAD51 paralog C)

RAD51C mutation • RAD51 mutation

carboplatin • paclitaxel • Zejula (niraparib)

4ms

Human Fallopian Tube-Derived Organoids with TP53 and RAD51D Mutations Recapitulate an Early Stage High-Grade Serous Ovarian Cancer Phenotype In Vitro. (PubMed, Int J Mol Sci)

TP53 and RAD51D co-deleted organoids exhibited heightened sensitivity to platinum, poly-ADP ribose polymerase inhibitors (PARPi), and cell cycle-related medication. In summary, our research highlighted the use of FTE organoids with RAD51D mutations as an invaluable in vitro platform for the early detection of carcinogenesis, mechanistic exploration, and drug screening.

4 months ago

Preclinical • Journal • PARP Biomarker

TP53 (Tumor protein P53) • RAD51D (RAD51 paralog D) • IL17A (Interleukin 17A)

TP53 mutation • TP53 deletion • RAD51D mutation • RAD51 mutation

4ms

Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor resistant advanced breast cancer. (PubMed, Ann Oncol)

These observations map the prevalence of candidate drivers of resistance across time in a clinical setting, information with implications for clinical management and trial design in HRD breast cancers.

4 months ago

Journal • BRCA Biomarker • PARP Biomarker • Metastases

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • RAD51 (RAD51 Homolog A) • RIF1 (Replication Timing Regulatory Factor 1) • TP53BP1 (Tumor Protein P53 Binding Protein 1)

TP53 mutation • HRD • PALB2 mutation • BRCA2 deletion • BRCA1 deletion • PARP1 mutation • RAD51 mutation

4ms

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 | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2022 --> Dec 2025

4 months ago

Trial completion date • Trial primary completion date • Surgery

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) • BARD1 (BRCA1 Associated RING Domain 1) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D) • FANCM (FA Complementation Group M)

BRCA2 mutation • BRCA1 mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • PPM1D mutation • FANCM mutation • RAD51 mutation

Lynparza (olaparib)

4ms

A Study to Evaluate Rucaparib in Combination With Other Anticancer Agents in Participants With a Solid Tumor (SEASTAR) (clinicaltrials.gov)

P1/2, N=25, Terminated, pharmaand GmbH | Phase classification: P1b/2 --> P1/2

4 months ago

Phase classification • Combination therapy

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

BRCA2 mutation • BRCA1 mutation • PALB2 mutation • RAD51C mutation • RAD51D mutation • RAD51 mutation

Rubraca (rucaparib) • Trodelvy (sacituzumab govitecan-hziy) • lucitanib (E 3810)

5ms

A Study of Olaparib and Pembrolizumab in People With Triple Negative Breast Cancer (TNBC) or Hormone Receptor-positive HER2-negative Breast Cancer (clinicaltrials.gov)

P2, N=23, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2024 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Jan 2026

5 months ago

Trial completion date • Trial primary completion date • Combination therapy

HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation • HR positive + HER-2 negative • PTEN mutation + HR positive • RAD51 mutation

Keytruda (pembrolizumab) • Lynparza (olaparib)

5ms

Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations (clinicaltrials.gov)

P1, N=108, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2024 --> Dec 2024 | Trial primary completion date: Jun 2024 --> Dec 2024

5 months ago

Trial completion date • Trial primary completion date • Metastases

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • CD4 (CD4 Molecule) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))

PIK3CA mutation • PTEN mutation • PALB2 mutation • CDK12 mutation • PIK3CA E545 • PIK3CA H1047 • BARD1 mutation • PIK3CA E542 • RAD51 mutation

Lynparza (olaparib) • Imfinzi (durvalumab) • Aliqopa (copanlisib)

5ms

Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations (clinicaltrials.gov)

P1, N=108, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

5 months ago

Enrollment closed • Metastases

PIK3CA mutation • PTEN mutation • PALB2 mutation • CDK12 mutation • PIK3CA E545 • PIK3CA H1047 • BARD1 mutation • PIK3CA E542 • RAD51 mutation

Lynparza (olaparib) • Imfinzi (durvalumab) • Aliqopa (copanlisib)

5ms

DIDO: Niraparib and Dostarlimab in HRD Solid Tumors (clinicaltrials.gov)

P2, N=30, Recruiting, West Cancer Center | Not yet recruiting --> Recruiting

5 months ago

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)

5ms

Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)

P1, N=30, Suspended, National Cancer Institute (NCI) | Initiation date: Oct 2023 --> Jul 2023

5 months ago

Trial initiation date

5ms

CERTIS1: Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies (clinicaltrials.gov)

P1/2, N=490, Recruiting, AstraZeneca | N=270 --> 490 | Trial primary completion date: Sep 2024 --> Apr 2025

5 months ago

Enrollment change • Trial primary completion date • Combination therapy • Metastases

BRCA2 mutation • BRCA1 mutation • HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation • RAD51 mutation

temozolomide • Enhertu (fam-trastuzumab deruxtecan-nxki) • datopotamab deruxtecan (DS-1062a) • AZD9574

6ms

Analysis of the indispensable RAD51 cofactor BRCA2 in Naganishia liquefaciens, a Basidiomycota yeast. (PubMed, Life Sci Alliance)

These phenotypes are indistinguishable from those of the rad51 mutant, and the rad51 brh2 double mutant. Naganishia Brh2 is likely the BRCA2 ortholog that functions as an indispensable auxiliary factor for Rad51.

6 months ago

Journal • BRCA Biomarker

BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A)

RAD51 mutation

6ms

Mutation spectrum, expression profiling, and prognosis evaluation of Fanconi anemia signaling pathway genes for 4259 patients with myelodysplastic syndromes or acute myeloid leukemia. (PubMed, BMC Med Genomics)

This investigation facilitates a deeper understanding of the functional links between FA and MDS/AML.

6 months ago

Journal

FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • FANCI (FA Complementation Group I)

FANCA mutation • RAD51 mutation

6ms

The mutational pattern of homologous recombination repair genes in urothelial carcinoma and its correlation with immunotherapeutic response. (PubMed, Cancer Med)

Our findings provide valuable insights into the genomic landscape of Chinese UC patients and underscore the molecular rationale for utilizing immunotherapy in UC patients with HRR mutations.

6 months ago

Journal • Tumor mutational burden • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • RAD51C (RAD51 paralog C)

PD-L1 expression • BRCA1 mutation • ATM mutation • CDK12 mutation • RAD51C mutation • BRCA2 mutation + ATM mutation • RAD51 mutation

MSK-IMPACT

6ms

Testing the Combination of the Anti-cancer Drugs Copanlisib, Olaparib, and MEDI4736 (Durvalumab) in Patients With Advanced Solid Tumors With Selected Mutations (clinicaltrials.gov)

P1, N=108, Recruiting, National Cancer Institute (NCI) | Phase classification: P1b --> P1

6 months ago

Phase classification • Metastases

PIK3CA mutation • PTEN mutation • PALB2 mutation • CDK12 mutation • PIK3CA E545 • PIK3CA H1047 • BARD1 mutation • PIK3CA E542 • RAD51 mutation

Lynparza (olaparib) • Imfinzi (durvalumab) • Aliqopa (copanlisib)

6ms

Whole Exome Sequencing reveals clinically important pathogenic mutations in DNA repair genes across lung cancer patients. (PubMed, Am J Cancer Res)

The observed pathogenic mutations in BRCA1, BRCA2, ERCC6, CHEK1, MUTYH, and RAD51D, coupled with their down-regulation and hypermethylation, suggest a potential convergence of genetic and epigenetic factors driving genomic instability in lung cancer cells. These findings contribute to our understanding of lung cancer susceptibility and highlight potential avenues for targeted therapeutic interventions in Pakistani lung cancer patients.

6 months ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • MUTYH (MutY homolog) • ERCC6 (Excision repair cross-complementation group 6)

BRCA2 mutation • BRCA1 mutation • RAD51D mutation • CHEK1 mutation • RAD51 mutation • CHEK1 expression

6ms

High-grade serous ovarian carcinoma, the "Achiles' hill" for clinicians and molecular biologists: a molecular insight. (PubMed, Mol Biol Rep)

For chemonaive patients, drugs that helps in efflux of reduced glutathione or prevent the redox coupling of GSH-GSSG, like Cisplatin, could be considered as the best therapeutic choice for HGSOC. For patients with BRCA1/2 mutations, PARP inhibitors alone or with Bevacizumab can be effective. Immune checkpoint inhibitors could be effective against immunoreactive subtypes. Identification of genes deregulated in chemoresistance could provide better insights in dealing with the disease.

6 months ago

Review • Journal • BRCA Biomarker • PARP Biomarker • IO biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • FOXM1 (Forkhead Box M1) • MIR1290 (MicroRNA 1290) • MIR23A (MicroRNA 23a) • RASSF1 (Ras Association Domain Family Member 1) • MIR205 (MicroRNA 205)

TP53 mutation • BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • RAD50 mutation • PARP1 mutation • RAD51 mutation • RASSF1 methylation

Avastin (bevacizumab) • cisplatin

6ms

Isolation and characterization of monomeric human RAD51: a novel tool for investigating homologous recombination in cancer. (PubMed, Angew Chem Int Ed Engl)

We investigated different buffers to identify the most suitable condition needed to definitively stabilize the monomer. The monomer of human RAD51 provides the community with a unique biological tool for investigating RAD51-mediated homologous recombination, and paves the way for more reliable structural, mechanistic, and drug discovery studies.

6 months ago

Journal • BRCA Biomarker

BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A)

RAD51 mutation

6ms

Cost-effectiveness analysis of RAD51 functional biomarker for platinum sensitivity in the GeparSixto trial (SABCS 2023)

The pharmacological costs were calculated following treatment protocol of GeparSixto where TNBC patients received neoadjuvant paclitaxel plus MyocetÂ®-nonpegylated liposomal doxorubicin (PM) or PM plus carboplatin (PMCb), both arms including bevacizumab. The most efficient scenarios are the functional RAD51 test and all comers. Both tBRCA1/2 and genomic HRD by Myriad MychoiceÂ® scenarios provide worse health outcomes at a higher cost, based on the data of the GeparSixto trial. This study highlights the potential overall benefit of functional HRD biomarkers to predict PARPi sensitivity.

6 months ago

HEOR • Cost-effectiveness • Cost effectiveness • PARP Biomarker • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A)

BRCA2 mutation • BRCA1 mutation • RAD51 mutation

Myriad myChoice® CDx

Avastin (bevacizumab) • carboplatin • paclitaxel • Myocet (non-pegylated liposomal doxorubicin)

6ms

The MAGIC study: Universal whole genome tumour and germline sequencing of newly diagnosed breast cancer identifies a high proportion of ER+ BRCA-like tumours (SABCS 2023)

Tumour sequencing identified three times as many cases that might be eligible for HR repair defect targeted therapy than germline testing alone (16% versus 5.2%). Unlike a previous study (Ann Oncol., 2019 30:1071-1079), the majority of the BRCA-like BCs were ER+ with no evidence of a VUS in a known HBC gene suggesting these are driven by novel germline or somatic mutations in genes involved in DNA HR repair.

6 months ago

BRCA Biomarker

ER (Estrogen receptor) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • BRCA (Breast cancer early onset) • 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) • BARD1 (BRCA1 Associated RING Domain 1)

ER positive • BRCA1 mutation • HRD • PALB2 mutation • HRD + BRCA1 mutation • RAD51C mutation • PMS2 mutation • RAD51 mutation

6ms

Unique molecular signatures of germline mutations in low expression of human epidermal growth factor receptor 2 (HER2) breast cancer (SABCS 2023)

HER2-low BC patients have distinct germline mutational signatures and differential clinical outcomes under neoadjuvant systemic therapy. These results have provided additional evidence that HER2-low patients comprise a fourth subtype of BC that needs to be accounted for separately in terms of clinical treatment and outcome reporting.

6 months ago

BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • MSH2 (MutS Homolog 2) • ERCC1 (Excision repair cross-complementation group 1) • PMS2 (PMS1 protein homolog 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • MRE11A (MRE11 homolog, double strand break repair nuclease) • MUTYH (MutY homolog) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FLCN (Folliculin) • FANCD2 (FA Complementation Group D2) • RECQL4( RecQ Like Helicase 4) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A) • RAD54B (RAD54 Homolog B)

BRCA1 mutation • EGFR mutation • HER-2 overexpression • HER-2 mutation • HER-2 expression • ATM mutation • PALB2 mutation • MSH2 mutation • RAD51C mutation • FANCA mutation • PMS2 mutation • FANCI mutation • FANCM mutation • RAD51 mutation • RECQL4 mutation

6ms

Molecular and immunological landscape of sex-based differences in breast cancer: a distinct disease in men. (SABCS 2023)

These data indicate that MaBC has a differential mutational frequency, copy number alteration, immune gene expression and immune cell infiltration and overall survival compared to their FeBC counterparts. A better understanding of these sex-based differences with additional research may help inform disease outcomes, provide a rationale for tailored therapeutic approaches and design future treatments. Table 1.

6 months ago

Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • ASXL1 (ASXL Transcriptional Regulator 1) • BCL6 (B-cell CLL/lymphoma 6) • KMT2D (Lysine Methyltransferase 2D) • RARA (Retinoic Acid Receptor Alpha) • WT1 (WT1 Transcription Factor) • FGF3 (Fibroblast growth factor 3) • CHEK2 (Checkpoint kinase 2) • CREBBP (CREB binding protein) • RAD51B (RAD51 Paralog B) • TSC1 (TSC complex subunit 1) • HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ Beta 1) • FOXA1 (Forkhead Box A1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • CHD1 (Chromodomain Helicase DNA Binding Protein 1) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D) • FLCN (Folliculin) • IL1A (Interleukin 1, alpha) • AMER1 (APC Membrane Recruitment Protein 1) • DAXX (Death-domain associated protein) • HLA-DQB2 (Major Histocompatibility Complex, Class II, DQ Beta 2)

TP53 mutation • MSI-H/dMMR • HER-2 negative • HER-2 mutation • STK11 mutation • ASXL1 mutation • ESR1 mutation • CREBBP mutation • AKT1 mutation • TSC1 mutation • MHC-II expression • FLCN mutation • RAD51 mutation

7ms

RAD51D Secondary Mutation-Mediated Resistance to PARP-Inhibitor-Based Therapy in HGSOC. (PubMed, Int J Mol Sci)

An acquired mutation can reverse a loss-of-function change in RAD51D and can result in PARPi resistance in a hereditary ovarian cancer patient. Liquid biopsy could be considered for longitudinal monitoring in ovarian patients under PARPi-based therapy, which can identify acquired resistant mutations earlier and facilitate precision management.

7 months ago

Journal • PARP Biomarker

RAD51D (RAD51 paralog D)

RAD51D mutation • RAD51 mutation

7ms

Genomic stability of prostate cancers with homologous recombination gene alterations (AMP 2023)

Prostate cancers with HRa exhibited higher genomic instability, as evidenced by an increased proportion of tumors with MSI-high and TMB-high status. Our findings demonstrate that BRCA1/2 alterations in particular are associated with increased genomic instability, and the lack of statistical differences between BRCAm and NBHRm groups suggests functional overlap between BRCA1/2 and non-BRCA1/2 HR genes. The correlation between HRa and MSI status may signify selection of HR pathway gene mutations in MSI-high tumors and warrants further investigation.

7 months ago

Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

BRCA2 mutation • BRCA1 mutation • TMB-H • MSI-H/dMMR • PALB2 mutation • FANCF mutation • RAD51 mutation

7ms

Clinical Utility of Homologous Recombination Deficiency (HRD) Profiling in Ovarian Cancer - An Indian Experience (AMP 2023)

This study profiles HRD status in the Indian population. It underscores the fact that BRCA1/2 mutational analysis alone cannot capture HRD positivity. Importantly, using an expanded HR panel did not identify additional mutations as potential causes of the observed HRD.

7 months ago

Clinical • BRCA Biomarker • PARP Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • CHEK2 (Checkpoint kinase 2)

TP53 mutation • HRD • PTEN mutation • BRCA1 positive • BRCA2 positive • RAD51 mutation

7ms

Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents (clinicaltrials.gov)

P1/2, N=466, Recruiting, AstraZeneca | Trial completion date: Feb 2026 --> Jun 2026 | Trial primary completion date: Feb 2026 --> Jun 2026

7 months ago

Trial completion date • Trial primary completion date • Combination therapy • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

HER-2 negative • HRD • PALB2 mutation • RAD51C mutation • BRCA mutation • RAD51 mutation

Lynparza (olaparib) • carboplatin • Imfinzi (durvalumab) • ceralasertib (AZD6738) • saruparib (AZD5305)

7ms

INHERITED LANDSCAPE AND A SPECIFIC RAD51D MUTATION OF CHINESE OVARIAN CANCER PATIENTS (IGCS 2023)

Only under the background of TP53 mutation, RAD51D K91fs mutation could increase the sensitivity to cisplatin. Overall, 31.1% (116/373) of patients harbored at least one pathogenic or likely pathogenic germline variant. BRCA1 and BRCA2 accounted for 16.09% and 5.36% respectively, with one patient harboring both mutations. Besides, 32 (8.58%) patients carried other HRR gene mutations, while 3 (0.8%) patients had MMR gene mutations.

7 months ago

Clinical • BRCA Biomarker • PARP Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • RAD51D (RAD51 paralog D)

TP53 mutation • BRCA2 mutation • BRCA1 mutation • RAD51D mutation • RAD51 mutation

cisplatin

7ms

In vivo reduction of RAD51-mediated homologous recombination triggers aging but impairs oncogenesis. (PubMed, EMBO J)

We propose that these in vivo phenotypes result from chronic endogenous replication stress caused by HR decrease, which preferentially targets progenitors and tumor cells. Our work underlines the importance of RAD51 activity for progenitor cell homeostasis, preventing aging and more generally for the balance between cancer and aging.

7 months ago

Preclinical • Journal

RAD51 (RAD51 Homolog A)

RAD51 mutation

7ms

Olaparib in Treating Patients With Metastatic Biliary Tract Cancer With Aberrant DNA Repair Gene Mutations (clinicaltrials.gov)

P2, N=36, Recruiting, Academic and Community Cancer Research United | Trial primary completion date: Mar 2024 --> Aug 2024

7 months ago

Trial primary completion date • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • ATR (Ataxia telangiectasia and Rad3-related protein) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PTEN mutation • ARID1A mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • BRCA mutation • NBN mutation • EMSY mutation • RAD51 mutation

Lynparza (olaparib)

8ms

Characterization of DNA Damage Response-Associated Somatic Mutations in Borderline Resectable and Locally Advanced Pancreatic Cancer. (PubMed, Int J Radiat Oncol Biol Phys)

Herein, we characterized the frequency of somatic mutations associated with DSB repair genes in patients with BRPC/LAPC. Data analysis on outcomes related to radiation response in patients with mutations in DDR pathways is ongoing, but will likely also benefit from multi-institutional efforts to increase the power to answer this question.

8 months ago

Journal • BRCA Biomarker • Metastases

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PALB2 (Partner and localizer of BRCA2) • SMAD4 (SMAD family member 4) • RAD51B (RAD51 Paralog B) • RAD50 (RAD50 Double Strand Break Repair Protein) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)

TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDKN2A mutation • SMAD4 mutation • RAD50 mutation • RAD51B mutation • BLM mutation • RAD54L mutation • NBN mutation • PRKDC mutation • RAD51 mutation

FoundationOne® CDx

gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium

8ms

Combining PARP and PD-1 inhibition in a patient with esophagogastric adenocarcinoma (EGA) (DGHO 2023)

In this case, a long-lasting response to the combination of olaparib and pembrolizumab was observed despite previous treatment with a PD-L1 inhibitor. This case illustrates the need for further clinical trials to analyze the efficacy of PARP inhibitor combinations in EGA.

8 months ago

Clinical • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • RAD51C (RAD51 paralog C) • FGF10 (Fibroblast Growth Factor 10)

PD-L1 expression • HER-2 positive • PD-L1 overexpression • RAD51C mutation • RAD51 mutation

Keytruda (pembrolizumab) • Lynparza (olaparib)