Topic 138

parp inhibitors ribose cancer parpi adp homologous brca1 poly inhibition repair recombination polymerase ovarian therapy dna inhibitor brca2 olaparib brca tumors rad51 cancers biology hr deficient mutated mutations lethality sensitivity platinum parp1 breast combination damage clinical pathway cytotoxicity treatment clinically targetable tumor veliparib depletion lines cells sensitive synthetic mutant response joining trials deficiency survival prostate atr rad51c lethal mek resistance serous pancreatic targeted double strand cisplatin upregulation patient increased mutation p53 agents relapsed patients vivo germline malignancies break therapies biomarker foci cgas alone toxic blocks pargi grade bard1 sting breaks parg hrd vitro tumours may poor inactivation radiation conversely parylation

27 items. Top items listed below.

Modulation of Early Mitotic Inhibitor 1 (EMI1) Depletion on the Sensitivity of PARP Inhibitors in BRCA1 Mutated Triple-Negative Breast Cancer Cells 138 126 14 10 3

PARP inhibition in Ewing sarcoma: impact of germline DNA damage repair defects and activation of immunoregulatory pathways 138 126 14 10 3

Role of PARylation and PTEN Mutation on PARP and PARG Inhibitor Efficacy on Glioblastoma 138 126 46 7 3

Polymerase Theta Inhibition Kills Homologous Recombination Deficient Tumors 138 126 14 10 3

Targeted DNA Damage Repair CRISPR/Cas9 Knockout Screen Identifies Novel Classification of Poly-ADP Ribose Polymerase Inhibitors Based on Key Base Excision Repair Proteins 138 126 33 14

Chromatin-Bound PARP1 Correlates with Upregulation of Inflammatory Genes in Response to Long-Term Treatment with Veliparib 138 126 14 10 3

CHK2 inhibition provides a strategy to suppress hematological toxicity from PARP inhibitors. 138 126 108 14 10 3

PARG inhibition induces replication catastrophe in ovarian cancer cells with down-regulated DNA replication genes 138 126 14 10 3

Pan-cancer landscape of homologous recombination deficiency 138 46 14 9

WNT inhibition creates a BRCA-like state in Wnt-addicted cancer 138 126 108 14 3

Wide-spectrum cancer killing by ENDOD1 ablation 138 46 14 10 3

Effects of germline and somatic events in candidate BRCAness genes on breast-tumor signatures 138 46 9

A meta-analysis of clinical cases of reversion mutations in BRCA genes identifies signatures of DNA end-joining repair mechanisms driving therapy resistance 138 126 14 9 3

ATR Inhibitors as Potent Modulators of DNA End Resection Capacity 138 46 3

Primary platinum resistance and immune exclusion in ovarian carcinomas with high expression of the homologous recombination mediator RAD51 138 14 10 9

ATM-deficient lung, prostate and pancreatic cancer cells are acutely sensitive to the combination of olaparib and the ATR inhibitor AZD6738 138 126 14 10 3

Cyclin E1 protein is stabilized in BRCA1 mutated breast cancers leading to synergy between CDK2 and PARP inhibitors 138 126 14 10 3

PARP1 inhibitors trigger innate immunity via PARP1 trapping-induced DNA damage response 138 14 3

Evaluating the Sensitivity of Sporadic Pancreatic Cancer to poly(ADP-ribose) polymerase (PARP) Inhibition (Velaparib, Olaparib, AG14361) as Single Agents and as Chemo-sensitizers 138 64 10

A small-molecule inhibitor of the BRCA2-RAD51 interaction modulates RAD51 assembly and potentiates DNA damage-induced cell death 138 46 3

Platinum resistance induces diverse evolutionary trajectories in high grade serous ovarian cancer 138 14 9 3

GATA3 and MDM2 are synthetic lethal in estrogen receptor-positive breast cancers 138 126 14 10 3

High-Throughput Functional Evaluation of BRCA2 Variants of Unknown Significance 138 97

The Genomic Landscape of Prostate Cancer Brain Metastases 138 14 9

CREBBP/EP300 mutation is associated with poor outcome in HNSCC and targetable with synthetic cytotoxicity. 138 126 14 10 3

ATR inhibition enhances 5-fluorouracil sensitivity independent of non-homologous end-joining and homologous recombination repair pathway 46 14 10 3

MEK inhibition causes Bim stabilization and sensitivity to Bcl2 family member inhibitors in RAS-MAPK mutated neuroblastoma 138 126 14 10 3

Pretreatment with LCK Inhibitors Chemosensitizes Cisplatin-Resistant Endometrioid Ovarian Tumors 138 126 14 10 3

ATM Inhibition Synergizes with Fenofibrate in High Grade Serous Ovarian Cancer Cells 126 14 10 9 3

Hyperactive end joining repair mediates resistance to DNA damaging therapy in p53-deficient cells 46 14 3

Poly(ADP-ribose)-binding and macroH2A mediate recruitment and functions of KDM5A at DNA lesions 46 31 3

PARP and PI3K inhibitor combination therapy eradicates c-MYC-driven murine prostate cancers via cGAS/STING pathway activation within tumor-associated macrophages 126 14 10 3

PARP1 and MGMT interaction-based sensitivity to DNA damage in Ewing sarcoma 126 14 10 3

The Dystonia Gene THAP1 Controls DNA Double Strand Break Repair Choice 46 3

Cavin3 released from caveolae interacts with BRCA1to regulate the cellular stress response 108 14 3

Integrated genomics and comprehensive validation reveal novel drivers of genomic evolution in esophageal adenocarcinoma 14 9 3

Discovery and Development of Novel DNA-PK Inhibitors by Targeting the unique Ku-DNA Interaction 46 33 3

Targeted CRISPR screening identifies PRMT5 as synthetic lethality combinatorial target with gemcitabine in pancreatic cancer cells 152 126 14 10 3

Structural variants at the BRCA1/2 loci are a common source of homologous repair deficiency in high grade serous ovarian carcinoma 97 9

Th17 cells contribute to combination MEK inhibitor and anti-PD-L1 therapy resistance in KRAS/p53 mutant lung cancers 126 14 10 3

Single-molecule measurements reveal that PARP1 condenses DNA by loop formation 163 8 3

Genome-wide CRISPR synthetic lethality screen identifies a role for the ADP- ribosyltransferase PARP14 in replication fork stability controlled by ATR 46 3

ARID2 deficiency promotes tumor progression and is associated with higher sensitivity to PARP inhibition in lung cancer 142 14 9 3

Gamma secretase inhibitors inhibit ovarian cancer development and enhance olaparib's anti-ovarian cancer activity and its mechanism 126 108 14 10 3

Dual genome-wide CRISPR knockout and CRISPR activation screens identify common mechanisms that regulate the resistance to multiple ATR inhibitors 108 14 3

Nicotinamide promotes differentiation of pancreatic endocrine progenitors from human pluripotent stem cells through poly (ADP-ribose) polymerase inhibition 57 20 3

Vulnerability of ARID1A deficient cancer cells to pyrimidine synthesis blockade 126 14 10 3

Homologous recombination defects in Shwachman-Diamond syndrome and Diamond-Blackfan anemia 46 3

Regulations of mitochondrial DNA repair by poly(ADP-Ribose) Polymerase 1 95 67 46 3

Massively parallel assessment of human variants with base editor screens 33 9

Dynamics of the HD regulatory subdomain of PARP 1; substrate access and allostery in PARP activation and inhibition. 63 46 8 3

The functional landscape of patient derived RNF43 mutations predicts Wnt inhibitor sensitivity 126 14 3

Hormonal regulation of Semaphorin 7a in ER+ breast cancer drives therapeutic resistance 126 14 10 3

A non-canonical EZH2 function sensitizes solid tumors to genotoxic stress 142 108 14 3

Store Independent Ca2+ Entry Regulates the DNA Damage Response in Breast Cancer Cells 108 14 10 3

Analysis of single-cell RNA-seq data from ovarian cancer samples before and after chemotherapy links stress-related transcriptional profile withchemotherapy resistance 14 9

Sustained Androgen Receptor signaling is a determinant of melanoma cell growth potential and tumorigenesis 108 14 10 3

Inhibition of USP28 overcomes Cisplatin-Resistance of Squamous Tumors by Suppression of the Fanconi Anemia Pathway. 126 14 3

MDM2 Inhibition in Combination with Endocrine Therapy and CDK4/6 Inhibition for the Treatment of ER-Positive Breast Cancer. 126 108 14 10 3

Somatic chromosomal number alterations affecting driver genes inform in-vitro and clinical drug response in high-grade serous ovarian cancer 126 14 10 9 3

ASH2L drives proliferation and sensitivity to bleomycin and other genotoxins in Hodgkin's lymphoma and testicular cancer cells 126 14 10 3

DNA methylation landscapes of matched primary and recurrent high grade serous ovarian cancers are preserved throughout disease progression and chemoresistance. 87 9

Cohesin mutations are synthetic lethal with stimulation of WNT signaling 108 14 3

Distinct pathways of homologous recombination controlled by the SWS1-SWSAP1-SPIDR complex 46 34 3

Loss of Caspase-8 function in combination with SMAC mimetic treatment sensitizes Head and Neck Squamous Carcinoma to radiation through induction of necroptosis 126 108 14 10 3

Longitudinal whole-exome sequencing of cell-free DNA unravels the metastatic evolutionary dynamics of BRCA2 mutated breast cancer 14 9

Biomarker-guided treatment strategies for ovarian cancer identified from a heterogeneous panel of patient-derived tumor xenografts 126 14 10 9

Ibrutinib blocks YAP1 activation and reverses BRAFi resistance in melanoma cells 126 14 10 3

Comparative gene expression in cells competent in or lacking DNA-PKcs kinase activity following etoposide exposure reveal differences in gene expression associated with histone modifications, inflammation, cell cycle regulation, Wnt signaling, and differentiation. 108 3

Platinum-Induced Ubiquitination of Phosphorylated H2AX by RING1A is Mediated by Replication Protein A in Ovarian Cancer 46 3

TCGA Pan-Cancer genomic analysis of Alternative Lengthening of Telomeres (ALT) related genes 9

BARD1 links histone H2A Lysine-15 ubiquitination to initiation of BRCA1-dependent homologous recombination 46 34 3

Inhibition of p-glycoprotein does not increase the efficacy of proteasome inhibitors in multiple myeloma cells 126 14 10 3

Replicated chromatin curtails 53BP1 recruitment in BRCA1-proficient and -deficient cells 46 34 3

PD-L1 lncRNA splice promotes lung adenocarcinoma progression via enhancing c-Myc activity 108 14 10 3

RRM2B is frequently amplified across multiple tumor types: non-oncogenic addiction and therapeutic opportunities 142 14 9 3

UBR-Box containing protein, UBR5, is over-expressed in human lung adenocarcinoma and is a potential therapeutic target 108 14 3

Reprogrammed mRNA translation drives resistance to therapeutic targeting of ribosome biogenesis 126 108 14 10 3

Taxane induces attenuation of the CXCR2/BCL-2 axis and sensitize prostate cancer to platinum-based treatments 126 14 10 3

Most commonly mutated genes in High Grade Serous Ovarian Carcinoma are nonessential for ovarian surface epithelial stem cell transformation 142 14 9

XAB2 prevents abortive recombinational repair of replication-associated DNA double-strand breaks and its loss is synthetic lethal with RAD52 inhibition 46 3

Antiviral Drug Screen of Kinase inhibitors Identifies Cellular Signaling Pathways Critical for SARS-CoV-2 Replication 44 1

Identification of Wee1 as Target in Combination with Avapritinib for the Treatment of Gastrointestinal Stromal Tumors 152 126 14 10 3

Neutralizing PD-L1 and PD-L2 Enhances the Efficacy of Immune Checkpoint Inhibitors in Ovarian Cancer. 126 14 10 3

A novel role for the tumor suppressor gene ITF2 in lung tumorigenesis and chemotherapy response 186 14 9 3

HDAC and MAPK/ERK inhibitors cooperate to reduce viability and stemness phenotype in medulloblastoma 186 108 14 10 3

A data-driven drug repositioning framework discovered a potential therapeutic agent targeting COVID-19 44 1

Epigenetic downregulation of HER2 during EMT leads to tumor resistance to HER2-targeted therapies in breast cancer 98 14 10 3

A 'one-two punch' therapy strategy to target chemoresistance in estrogen receptor positive breast cancer 152 126 14 10 3

Topsentinol L Trisulfate, a new Marine Natural Product, that Targets Basal-like and Claudin-low Breast Cancers 126 14 10 9 3

225Ac-labeled CD33-targeting antibody reverses resistance to Bcl-2 inhibitor venetoclax in acute myeloid leukemia models 126 14 10 3

The Molecular Landscape of Asian Breast Cancers Reveals Clinically Relevant Population-Specific Differences 14 9

Beta 1 Integrin Signaling Mediates Pancreatic Ductal Adenocarcinoma Resistance to MEK Inhibition 126 108 14 10 3

The novel reversible LSD1 inhibitor SP-2577 promotes anti-tumor immunity in SWItch/Sucrose-NonFermentable (SWI/SNF) complex mutated ovarian cancer 14 3

Both DNA binding domains of p53 are required for its ultra rapid recruitment to sites of UV damage 46 34 3

Inhibition of CAMKK2 impairs autophagy and castration-resistant prostate cancer via suppression of AMPK-ULK1 signaling 108 14 3

RIPK2 Stabilizes c-Myc and is an Actionable Target for Inhibiting Prostate Cancer Metastasis 108 14 10 3

Transcriptional control of DNA repair networks by CDK7 regulates sensitivity to radiation in Myc-driven Medulloblastoma 108 14 3

HIV Vpr modulates the host DNA damage response at two independent steps to damage DNA and repress double-strand DNA break repair 46 41 3

Overcoming resistance to immune checkpoint therapy in PTEN-null prostate cancer by sequential intermittent anti-PI3Ka/b/δ and anti-PD-1 treatment 126 14 10 3