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PARP2 (Poly(ADP-Ribose) Polymerase 2)

News alerts, weekly reports and conference planners

11d

The Contribution of Genetic Modifiers to Ovarian Cancer Risk in BRCA1 and BRCA2 Pathogenic Variant Carriers. (PubMed, Cancers (Basel))

The analysis identified 11 variants affecting both BRCA1 and BRCA2 carriers, most of which increase risk, including the following: IRS1, RSPO1, SYNPO2, BABAM1, MRPL34, PLEKHM1, and TIPARP...The only SNP reaching genome-wide significance (p < 5 × 10-8) was in BNC2. The article summarizes the growing number of genetic modifiers of ovarian cancer risk among BRCA1/2 carriers and highlights their potential to improve individualized risk assessment, enhance patient stratification, support personalized prevention and surveillance strategies, deepen the understanding of disease biology, and identify potential therapeutic targets.

11 days ago

Review • Journal

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRAS (Harvey rat sarcoma viral oncogene homolog) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • MTHFR (Methylenetetrahydrofolate Reductase) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • CASP8 (Caspase 8) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • RSPO1 (R-Spondin 1) • TIPARP (TCDD Inducible Poly(ADP-Ribose) Polymerase) • ITGB3 (Integrin Subunit Beta 3)

12d

Design, synthesis and biological evaluation of novel pyrrolo[1,2-b]pyridazin-2(1H)-ones as selective PARP1 inhibitors for cancer therapy. (PubMed, Eur J Med Chem)

Also, YCH3971 possessed a strong antiproliferative activity on BRCA mutant MDA-MB-436 cells with an IC50 of 2.10 nM. However, since the oral bioavailability of YCH3971 in rats is only 1.2%, we have not yet initiated in vivo efficacy studies.

12 days ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA (Breast cancer early onset) • PARP2 (Poly(ADP-Ribose) Polymerase 2)

BRCA mutation

18d

Discovery of novel olaparib-β-carboline hybrids for treating BRCA-deficient triple negative breast cancer. (PubMed, Bioorg Med Chem)

Mechanistically, compound 6 could increase DNA damage, induce cell cycle arrest in the G2/M phase, and promote MDA-MB-436 apoptosis. Overall, 6 is a potential hybrid molecule and can be a candidate compound for the treatment of BRCA-deficient TNBC.

18 days ago

Journal

BRCA (Breast cancer early onset) • PARP2 (Poly(ADP-Ribose) Polymerase 2)

Lynparza (olaparib)

Fluzoparib as Adjuvant Treatment in Patients With Germline Homologous Recombination Repair (HRR) Mutated Primary Breast Cancer (Flamenco) (clinicaltrials.gov)

P2, N=334, Not yet recruiting, Fudan University

1 month ago

New P2 trial • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCM (FA Complementation Group M) • RAD52 (RAD52 Homolog DNA Repair Protein) • RPA1 (Replication Protein A1) • PARP2 (Poly(ADP-Ribose) Polymerase 2)

HER-2 negative • PALB2 mutation • PGR positive • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation

capecitabine • AiRuiYi (fluzoparib)

The effect of dimeric bisbenzimidazoles on the activity of DNA repair enzymes TDP1, TDP2, PARP1 and PARP2. (PubMed, Vavilovskii Zhurnal Genet Selektsii)

According to the results of modeling, the inhibitors are located in the binding region of the 3'-end of DNA in the active site of TDP1 and could form stable bonds with the catalytically significant TDP1 residues His263 and His493. These interactions probably provide the high inhibitory activity of the compounds observed in biochemical experiments.

1 month ago

Journal

PARP1 (Poly(ADP-Ribose) Polymerase 1) • PARP2 (Poly(ADP-Ribose) Polymerase 2)

2ms

PARP1 and PARP2 are dispensable for DNA repair by microhomology-mediated end-joining at double-ended DSBs. (PubMed, Nucleic Acids Res)

Importantly, we show that PARP1 and 2 are dispensable for MMEJ at double-ended DSBs (deDSBs) and is expendable for repair of DSBs during mitosis. Altogether, this data shifts the understanding of the role of PARP1 in MMEJ and DNA repair pathway choice and further strengthens a rationale for PARPi/MMEJi combinatorial drug treatment in HR-deficient cancers.

2 months ago

Journal

HRD (Homologous Recombination Deficiency) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • PARP2 (Poly(ADP-Ribose) Polymerase 2)

HRD

2ms

Replication-associated base excision repair/single-strand break repair regulates PARG inhibitor response via the PRMT1/PRMT5/ATR axis. (PubMed, NAR Cancer)

Finally, inhibition of the ATR regulators PRMT1 or PRMT5 synergizes with PARG inhibition, implicating replication-associated BER/SSBR and PARylation in the activation of the PRMT1/PRMT5/ATR axis. This study highlights the role of BER/SSBR in protecting the cell during S-phase to suppress PARylation-induced checkpoint activation, which may suggest a potential intervention strategy for PARG inhibitor-resistant tumors.

2 months ago

Journal

CHEK1 (Checkpoint kinase 1) • PRMT1 (Protein Arginine Methyltransferase 1) • POLG2 (DNA Polymerase Gamma 2, Accessory Subunit) • XRCC1 (X-Ray Repair Cross Complementing 1) • LIG3 (DNA Ligase 3) • PARP2 (Poly(ADP-Ribose) Polymerase 2)

2ms

PARPs and PARP inhibitors: molecular mechanisms and clinical applications. (PubMed, Mol Biomed)

Clinically, PARP inhibitors (PARPi), such as olaparib, niraparib, rucaparib, and talazoparib, exploit synthetic lethality in homologous recombination-deficient tumors and are increasingly applied in ovarian, breast, prostate, and pancreatic cancers. By integrating canonical DNA repair roles with non-canonical signaling and host-virus interactions, PARPs represent pivotal regulators. Similarly, the versatile therapeutics of PARPi have implications that extend beyond oncology into a broader and diverse range of other human diseases.

2 months ago

Review • Journal • PARP Biomarker

HRD (Homologous Recombination Deficiency) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3)

Lynparza (olaparib) • Talzenna (talazoparib) • Zejula (niraparib) • Rubraca (rucaparib)

2ms

Multi-cohort analysis and experimental study on the function of squalene epoxidase as a ferroptosis inhibitor in HCC. (PubMed, BMC Cancer)

Knockdown of PARP2 significantly mitigated SQLE-induced cholesterol accumulation and cellular proliferation. This study illustrates the role of SQLE as a ferroptosis inhibitor in HCC, offering novel insights into the prognostic evaluation and molecular mechanisms underlying HCC.

2 months ago

Journal • PARP Biomarker

PARP2 (Poly(ADP-Ribose) Polymerase 2) • SQLE (Squalene Epoxidase)

4ms

Molecular Dynamics and Energetic Insights into Novel PARP15 Inhibitors: A Structural Approach for Targeting BRCA-Mutated Breast Cancer. (PubMed, Curr Pharm Des)

Three compounds, F2002-0551, F2028-0309, and F1495-1822, emerged with docking scores surpassing the known PARP15 inhibitor, Niraparib... F2002-0551, F2028-0309, and F1495-1822 represent promising leads for PARP15 inhibition. This study offers a computational foundation for future experimental validation and therapeutic exploration in BRCA-associated breast cancer.

4 months ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • PARP2 (Poly(ADP-Ribose) Polymerase 2)

BRCA mutation

Zejula (niraparib)