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GENE:

RAD54L (DNA Repair And Recombination Protein RAD54)

News alerts, weekly reports and conference planners

10d

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.

10 days ago

Journal

HRD (Homologous Recombination Deficiency) • RAD54L (DNA Repair And Recombination Protein RAD54) • LIG3 (DNA Ligase 3)

26d

KNIGHTS: High-Risk Metachronous Oligometastatic Prostate Cancer Trial (clinicaltrials.gov)

P2, N=88, Recruiting, University of Maryland, Baltimore | Not yet recruiting --> Recruiting

26 days ago

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

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.

1 month ago

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 • Votrient (pazopanib) • Torisel (temsirolimus) • Inlyta (axitinib)

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

1 month ago

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)

2ms

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

2 months ago

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)

2ms

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

2 months ago

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)

3ms

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

3 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

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.

3 months ago

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)

3ms

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.

3 months ago

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

3ms

A Study Evaluating Safety and Efficacy of Niraparib in Patients With Previously Treated Metastatic Esophageal/Gastroesophageal Junction/Proximal Gastric Adenocarcinoma (clinicaltrials.gov)

P2, N=43, Active, not recruiting, Shadia Jalal, MD | Trial completion date: Nov 2024 --> Jul 2024 | Trial primary completion date: Nov 2023 --> Feb 2023

3 months ago

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)

3ms

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

3 months ago

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

4ms

KNIGHTS: High-Risk Metachronous Oligometastatic Prostate Cancer Trial (clinicaltrials.gov)

P2, N=88, Not yet recruiting, University of Maryland, Baltimore

4 months ago

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 • prednisone

5ms

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

5 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)

5ms

Pembrolizumab, Olaparib, and Temozolomide for People With Glioma (clinicaltrials.gov)

P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center

5 months ago

Trial completion date • Trial primary completion date

CDKN2A deletion • BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type

Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide

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

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.

5 months ago

Journal

RAD54L (DNA Repair And Recombination Protein RAD54) • FERMT1 (Fermitin Family Member 1)

5ms

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.

5 months ago

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

5ms

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.

5 months ago

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

5ms

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 â‰¥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.

5 months ago

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 capsule) • abiraterone acetate

5ms

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

5 months ago

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)

6ms

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.

6 months ago

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

6ms

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.

6 months ago

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

6ms

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.

6 months ago

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

6ms

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

6 months ago

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)

6ms

The role of DNA repair genes mutational status in prostate cancer treatment with androgen signaling blockade (EMUC 2023)

Probably, the data obtained on the worst efficacy of enzalutamide after docetaxel in patients with mutations in HRR genes can be attributed to the biological features of the influence of therapy methods on the course of the disease. In clinical practice, it is advisable to take into account the fact of the influence of previous treatment on the effectiveness of antiandrogenic therapy in choosing the sequence of treatment methods.

6 months ago

BRCA Biomarker

KRAS (KRAS proto-oncogene GTPase) • 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) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51B mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression

docetaxel • Xtandi (enzalutamide capsule)

7ms

miR-3200 accelerates the growth of liver cancer cells by enhancing Rab7A. (PubMed, Noncoding RNA Res)

Furthermore, our results suggest that miR-3200 enhances expression of RAB7A, and then Rab7A regulates the carcinogenic function of miR-3200 by increasing telomere remodeling in human liver cancer. These results are of great significance for the prevention and treatment of human liver cancer.

7 months ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • CCND1 (Cyclin D1) • SQSTM1 (Sequestosome 1) • PIM1 (Pim-1 Proto-Oncogene) • RAD54L (DNA Repair And Recombination Protein RAD54) • ARAF (A-Raf Proto-Oncogene) • PCNA (Proliferating cell nuclear antigen) • ANXA6 (Annexin A6) • CDK1 (Cyclin-dependent kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • HOXC8 (Homeobox C8) • HSPA1A (Heat Shock Protein Family A (Hsp70) Member 1A) • MIR3200 (MicroRNA 3200) • PLK2 (Polo Like Kinase 2) • BECN1 (Beclin 1) • CDC45 (Cell Division Cycle 45) • FBXO32 (F-Box Protein 32) • FZD3 (Frizzled Class Receptor 3) • ITGB5 (Integrin Subunit Beta 5) • MAD2L1 (Mitotic Arrest Deficient 2 Like 1) • PKM (Pyruvate Kinase M1/2) • RAB7A (RAB7A, Member RAS Oncogene Family) • SUV39H1 (SUV39H1 Histone Lysine Methyltransferase) • ABCE1 (ATP Binding Cassette Subfamily E Member 1)

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

Pan-Cancer Analysis of Oncogenic Role of RAD54L and Experimental Validation in Hepatocellular Carcinoma. (PubMed, J Inflamm Res)

RAD54L exhibits robust expression in both pan-cancer and HCC, exerting a significant influence on the proliferation and migration of HCC cells. These findings highlight its potential as a promising biomarker for pan-cancer and a prospective target for immunotherapy.

8 months ago

Journal • Tumor mutational burden • IO biomarker • Pan tumor

TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency) • RAD54L (DNA Repair And Recombination Protein RAD54) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)

8ms

Ovarian High-grade Serous Carcinoma with Transitional-like (SET) Morphology: A Homologous Recombination-deﬁcient Tumor. (PubMed, Hum Pathol)

"Our results show that the majority of HGSCs with SET features are homologous recombination deficient tumors independently of the BRCA status and highlight the importance of the homologous recombination repair tumor testing especially in BRCA wild-type tumors. Recognition of transitional cell variant of HGSCs may help to identify patients most likely to benefit from PARP inhibitors."

8 months ago

Journal

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) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)

BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • BRCA wild-type • CDK12 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression

Myriad myChoice® CDx Plus • SOPHiA DDM HRD Solution

9ms

DOLAF: Durvalumab, With Olaparib and Fulvestrant in Advanced ER+, HER2- Breast Cancer Patients. (clinicaltrials.gov)

P2, N=172, Active, not recruiting, UNICANCER | Recruiting --> Active, not recruiting

9 months ago

Enrollment closed • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • 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) • RAD51C (RAD51 paralog C) • CHEK1 (Checkpoint kinase 1) • 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)

ER positive • BRCA1 mutation • HER-2 negative • FANCA deletion

Lynparza (olaparib) • Imfinzi (durvalumab) • fulvestrant

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: Jan 2024 --> May 2024 | Trial primary completion date: Jul 2023 --> Nov 2023

9 months ago

Trial completion date • Trial primary completion date • Metastases

BRIP1 mutation

Rubraca (rucaparib) • Aliqopa (copanlisib)

9ms

Characterization of DNA Damage Response-Associated Somatic Mutations in Borderline Resectable and Locally Advanced Pancreatic Cancer (ASTRO 2023)

Chemotherapy consisted of modified FOLFIRINOX or gemcitabine/nab-paclitaxel, and patients were treated with SBRT in 33 Gy in 5 fractions... Herein, we characterized the frequency of somatic mutations associated with DSB repair genes in patients with BRPC/LAPC. Data analysis on outcomes related to radiation response in patie nts with mutations in DDR pathways is ongoing, but will likely also benefit from multi-institutional efforts to increase the power to answer this question .

9 months ago

BRCA Biomarker • Metastases

FoundationOne® CDx

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

9ms

MATRIX: I/II Phase Study Evaluating M1774 in Combination With Fulvestrant in HR+ and HER2- Advanced Breast Cancers (clinicaltrials.gov)

P1/2, N=57, Not yet recruiting, Institut Paoli-Calmettes

9 months ago

New P1/2 trial • Combination therapy • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • 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) • 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) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCD2 (FA Complementation Group D2) • XRCC1 (X-Ray Repair Cross Complementing 1)

BRCA2 mutation • HR positive • HER-2 negative • ATM mutation • ARID1A mutation • PALB2 mutation

fulvestrant • tuvusertib (M1774)

10ms

A prospective study to determine the prevalence of DNA repair defects in patients (pts) with advanced prostate cancer (PC) (ESMO 2023)

PREVALENCE test results were also used to assess biomarker eligibility for niraparib interventional studies: MAGNITUDE (NCT03748641) and AMPLITUDE (NCT04497844)...The frequency of HRR+ was highest in pts tested by tumor tissue. PREVALENCE demonstrates the feasibility of prospective genetic testing to identify PC pts who benefit most from a precision oncology approach.

10 months ago

Clinical • BRCA Biomarker • PARP Biomarker • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • 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)

BRCA mutation

Zejula (niraparib)

10ms

PARPiPANC: A multicentric, single arm, phase II assessing niraparib as first line therapy for patients with metastatic homologous repair-deficient pancreatic cancer (ESMO 2023)

Correlative studies include documentation of HR alteration at time of progression on optional de novo tumor biopsy as well as assessment of predictive value for niraparib resistance of existing or new variants using liquid biopsies. To date, 4 French hospitals are participating.

10 months ago

Clinical • P2 data • BRCA Biomarker • PARP Biomarker • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • 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) • MRE11A (MRE11 homolog, double strand break repair nuclease) • 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)

BRCA2 mutation • BRCA1 mutation • BRIP1 mutation • FANCA mutation • NBN mutation

Zejula (niraparib)

10ms

Homologous recombination repair (HRR) gene mutation: A novel biomarker for precision genomics testing in advanced lung cancer (ESMO 2023)

Table: 1429P Conclusions The HRR gene mutation in advanced lung cancer was independent of the predictors for immunotherapy response (TMB, MSI and PD-L1 biomarkers). Further clinical trials are needed to assess the efficacy of combining poly ADP ribose polymerase (PARP) inhibitors with immunotherapy in the future.

10 months ago

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

TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • 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) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)

BRCA2 mutation • ATM mutation • ARID1A mutation • CDK12 mutation • BRIP1 mutation • FANCA mutation • RAD51B mutation • BARD1 mutation • BRCA mutation • CHEK1 mutation • CHEK1 expression

FoundationOne® CDx

10ms

Implications of KMT2C knockdown for DNA damage repair in breast cancer (ESMO 2023)

Conclusions KMT2C loss-of-function in breast cancer may impact DNA damage response pathways including homologous recombination and therefore be implicated in response to established treatments such as PARP-inhibitors. Further study including mapping of co-dependencies by whole genome siRNA screens in KMT2C-mutant breast cancer cells to identify synthetic lethality targets, as well as cell toxicity assays, are being performed in light of these results.

10 months ago

BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • KMT2C (Lysine Methyltransferase 2C) • RAD51 (RAD51 Homolog A) • RAD54L (DNA Repair And Recombination Protein RAD54) • POLD3 (DNA Polymerase Delta 3)

KMT2C mutation • MLL3 mutation

10ms

HRR Gene Mutations- A New Biomarker for Precision Genomics Based Testing in Metastatic Lung Cancer (IASLC-WCLC 2023)

The emphasis on precision genomics-based targeted therapy in metastatic lung cancer is evolving rapidly and the addition of new HRR genes-based biomarker testing in lung cancer promotes opportunity for further clinical trials to assess the efficacy of combining PARP inhibitors with Immunotherapy in the future.

10 months ago

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

PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • 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) • 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) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • IL1R1 (Interleukin 1 receptor, type I) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)

PD-L1 expression • BRCA2 mutation • BRCA1 mutation • MSI-H/dMMR • ATM mutation • ARID1A mutation • PD-L1 negative • PALB2 mutation • CDK12 mutation • CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • BRCA mutation • CHEK1 mutation • FANCG mutation • RAD51 mutation • CHEK1 expression

FoundationOne® CDx

11ms

Real-World Evidence of Germline Alterations in Women with Breast and Ovarian Cancer beyond BRCA1 and BRCA2 from a South Asian Population (AMP Europe 2023)

Key findings from this study demonstrate nearly 53% of the individuals with the clinical phenotype of hereditary breast and ovarian cancers are BRCA negative. However, they possess genetic alterations other than BRCA1/2 genes, which are associated with cancer risk predisposition. This study summarizes the findings of >200 cases of several intriguing familial presentation with non- syndromic genetic alterations in pathways such as DNA repair, receptor tyrosine kinase, cellular metabolism, chromatin remodeling, and Wnt/beta-catenin.

11 months ago

Clinical • HEOR • Real-world evidence • BRCA Biomarker • Real-world

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • RAD54L (DNA Repair And Recombination Protein RAD54) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D) • CTNNA1 (Catenin Alpha 1) • FANCM (FA Complementation Group M) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • RAD54L mutation • FANCM mutation

11ms

The Curcumin Analog PAC Is a Potential Solution for the Treatment of Triple-Negative Breast Cancer by Modulating the Gene Expression of DNA Repair Pathways. (PubMed, Int J Mol Sci)

In silico analysis of gene-gene interaction shows that there are common genes between MCF-7 and MDA-MB-321 having direct and indirect effects, among them via coexpression, genetic interactions, pathways, predicted and physical interactions, and shared protein domains with predicted associated genes indicating they are more likely to be functionally related. Our data show that PAC increases involvement of multiple genes in a DNA repair pathway, this certainly can open a new perspective in breast-cancer treatment.

11 months ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • ERCC1 (Excision repair cross-complementation group 1) • ERCC2 (Excision repair cross-complementation group 2) • RAD51D (RAD51 paralog D) • RAD54L (DNA Repair And Recombination Protein RAD54) • LRIG1 (Leucine Rich Repeats And Immunoglobulin Like Domains 1) • ATP23 (ATP23 Metallopeptidase And ATP Synthase Assembly Factor Homolog) • FEN1 (Flap Structure-Specific Endonuclease 1) • XRCC3 (X-Ray Repair Cross Complementing 3)

BCL2 expression

12ms

Phase II Trial of the PARP Inhibitor Niraparib and PD-1 Inhibitor Dostarlimab in Patients With Advanced Cancers With Active Progressing Brain Metastases (STARLET) (clinicaltrials.gov)

P2, N=120, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

12 months ago

Enrollment open • Metastases

PD-L1 (Programmed death ligand 1) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog 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) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • RAD52 (RAD52 Homolog DNA Repair Protein)

PD-L1 expression

Zejula (niraparib) • Jemperli (dostarlimab-gxly)

1year

Exploring the prognostic and predictive impact of genomic loss of heterozygosity (LOH) in metastatic colorectal cancer (mCRC) patients (ESMO-GI 2023)

P2 | "Both these trials assessed the combination of an anti-PDL1 (atezolizumab or avelumab) with the triplet FOLFOXIRI plus bevacizumab or cetuximab... In MSS mCRC, LOH-high was associated with biallelic alterations in the HRR system, worse prognosis and higher benefit from the addition of anti-PDL1 agents to chemotherapy. Considering the low number of LOH-high tumors in our study, these results deserve confirmation in larger cohorts."

1 year ago

Clinical

BRAF (B-raf proto-oncogene) • ABL1 (ABL proto-oncogene 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency) • DNMT3A (DNA methyltransferase 1) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • 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) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • RBBP8 (RB Binding Protein 8, Endonuclease) • XRCC2 (X-Ray Repair Cross Complementing 2) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • RAD52 (RAD52 Homolog DNA Repair Protein) • FANCG (FA Complementation Group G) • FANCC (FA Complementation Group C)

MSI-H/dMMR • BRAF mutation

FoundationOne® CDx

Avastin (bevacizumab) • Erbitux (cetuximab) • Tecentriq (atezolizumab) • 5-fluorouracil • Bavencio (avelumab) • oxaliplatin • irinotecan • leucovorin calcium