PARP inhibition in cancer therapy

An auto-generated ADP-ribosyl-cysteine degron drives DTX2-dependent turnover of PARP7

This study identifies an ADP-ribosyl-cysteine degron in PARP7 that is recognized by DTX2, leading to PARP7 degradation and affecting AR signaling in prostate cancer.

Small molecules targeting BRCA1-deficient cancer cells

The paper identifies small molecules that induce apoptosis in BRCA1-deficient cancer cells and links PPAR beta/delta inhibition to poor survival in breast cancer patients.

Predicting resistance to synthetic lethal therapies in cancer

This paper develops a model to predict resistance to synthetic lethal therapies by integrating protein-protein interaction networks with molecular profiles from CRISPR screens.

Targeting ribosome biogenesis sensitizes PARPi-resistant triple-negative breast cancer

This study shows that combining PARPi with ribosome biogenesis inhibitors sensitizes PARPi-resistant triple-negative breast cancer cells and identifies ribosome biogenesis as a therapeutic target.

Dimerization of human PARP15 is required for NAD+ binding and automodification

This study shows that dimerization of PARP15 is necessary for NAD+ binding and automodification, supported by structural and biochemical evidence.

PGG Enhances Olaparib Efficacy via cGAS-STING Signaling and Sensitizes Triple-Negative Breast Cancer to PD- L1 Blockade

This study shows PGG enhances olaparib efficacy in TNBC by inducing HRD and activates cGAS-STING to sensitize tumors to PD-L1 blockade, converting 'cold' to 'hot' tumors.

Catalytically inactive PARP1 protein drives PARP inhibitor induced hematological toxicity

This study shows that catalytically inactive PARP1, not PARP2, is responsible for PARP inhibitor-induced hematological toxicity in mice.

Cellular uptake of folate-olaparib conjugates via folate receptor-mediated endocytosis: Potential for selective delivery of DNA damage response inhibitors into tumour cells

This paper develops folate-olaparib conjugates that selectively enter FR-overexpressing tumor cells via endocytosis and inhibit PARylation.

Longitudinal transcriptomic analysis reveals adaptive transcript usage remodeling associated with PARP inhibitor resistance

This study identifies transcript usage remodeling in PARPi-resistant ovarian cancer through longitudinal RNA-sequencing, showing distinct patterns in acquired vs. innate resistance.

Chronic Alcohol Exposure Induces Persistent DNA Damage Response Signaling and Sensitizes Breast Epithelial Cells to PARP Inhibition

This study shows chronic alcohol exposure causes lasting DNA damage and makes breast cells more sensitive to PARP inhibitors.

TALAVE in Breast Cancer: BRCA1/2 Mutation-Dependent Immune Remodeling after PARP Inhibition with Limited Checkpoint Engagement

The paper shows BRCA-mutant breast cancers respond to PARP inhibitors with immune remodeling, but PD-L1 blockade is ineffective due to spatial separation of PD-L1+ cells and PD-1+ T cells.

PARP16 is a Druggable Regulator of Ribosome MARylation and Protein Homeostasis in Ovarian Cancer Cells

This study investigates PARP16's role in ovarian cancer by showing that inhibiting it with DB008 disrupts ribosome MARylation, impairs protein homeostasis, and reduces tumor growth.

Residual cohesin function and PARP1 levels determine PARP inhibitor sensitivity in STAG2-deficient cancers

This study identifies residual cohesin function and PARP1 levels as key factors determining PARP inhibitor sensitivity in STAG2-deficient cancers, highlighting the need for biomarker-based patient stratification.

Drug-induced nuclear cathepsin L (nCTSL) defines a targetable DNA damage response axis and PARP inhibitor sensitivity in ovarian cancer

This study identifies nuclear cathepsin L (nCTSL) as a biomarker for PARP inhibitor sensitivity in ovarian cancer and shows that combining clofarabine with PARP inhibitors enhances therapeutic response.

DePARylation prevents DNA replication-driven PARP1 condensation

This study shows that PARG inhibition leads to PARP1 condensation during DNA replication, highlighting Okazaki fragment maturation as a target for enhancing PARGi cytotoxicity.

KLF4 promotes apoptosis evasion and PARP inhibitor resistance in BRCA2-mutated epithelial ovarian cancer

This study identifies KLF4 as a driver of apoptosis evasion and PARP inhibitor resistance in BRCA2-mutated ovarian cancer, showing that targeting KLF4 enhances olaparib efficacy.

Replication fork plasticity is a therapeutic vulnerability in acute myeloid leukemia

This study identifies replication fork plasticity as a key determinant of therapy response in AML, showing that PrimPol mediates resistance to PARPi and araC.

Augmenting Radiation Sensitivity by Targeting PAR-Dependent Replication Fork Vulnerability in IDH-Mutant Glioma

This study shows that inhibiting PARG enhances radiosensitivity in IDH1-mutant glioma cells by disrupting PAR-dependent replication fork processes and S-phase kinetics.

Genomic alterations enable BRCA1 methylation loss and promoter bypass to drive resistance in high-grade serous ovarian cancer

This study identifies genomic mechanisms enabling BRCA1 methylation loss and promoter bypass in ovarian cancer, leading to PARP inhibitor resistance.

STN1 upregulation promotes PARPi resistance in BRCA2-deficient cancer cells via replication fork protection and suppression of ssDNA gap formation

This study identifies STN1 as a factor promoting PARPi resistance in BRCA2-deficient cancer cells by stabilizing replication forks and reducing ssDNA gaps.

MicroRNA spatial profiling for assessing drug efficacy in BRCA1-related triple-negative breast tumors

Latent Dirichlet allocation topics from hydrogel-array spatial miRNA maps of day-10 treated K14-Cre Brca1/Trp53 mouse breast tumors separated olaparib-sensitive (miR-21-dominated) from resistant (let-7a-dominated) tumors.

PARP1 inhibition regulates tumor progression through modulation of RhoGDIα and vimentin in triple negative breast cancer

This study shows PARP1 inhibition reduces metastasis in TNBC by regulating RhoGDIα and vimentin expression and cytoskeletal rearrangement.

Transposable elements shape olaparib response according to BRCA1 status in triple-negative breast cancer

This paper shows that olaparib treatment increases transposable element activity in BRCA1-deficient triple-negative breast cancer cells, leading to genomic instability and immune responses.

Leveraging Homologous Recombination Deficiency via the Repositioned Prodrug CB1954

This paper identifies CB1954 as a selective therapy for BRCA2-deficient cancers by showing its activity in HRD cells and mechanism of action.

Targeting Cellular Pseudo-Senescence to Overcome PARP inhibitors Resistance in BRCA1 -Mutated Breast Cancer

This study identifies ZNF251 deficiency as a driver of PARP inhibitor resistance in BRCA1-mutant breast cancer, showing that targeting pseudo-senescence with senomorphic or senolytic therapies can overcome resistance.

Targeting THOC2-Mediated mRNA Export Induces PARP Inhibitor Vulnerability in DNA Repair-Competent Hepatocellular Carcinoma

This study identifies THOC2 as a regulator of DNA repair and growth in HCC, showing that targeting THOC2 enhances PARPi efficacy by disrupting mRNA export of DDR genes.

Nucleophagy removes cytotoxic trapped PARP1

This study identifies nucleophagy as the mechanism by which trapped PARP1 is cleared, showing that inhibiting this process re-sensitizes PARPi-resistant cells to PARPi.

Mapping the Subtype-Specific PARP1 ADP-ribosylated Proteome in Breast Cancer Cells

The paper maps PARP1 ADP-ribosylated proteomes in breast cancer subtypes, identifying subtype-specific modifications and their functional implications.

Landscape of reversion alterations in homologous recombination genes reveals evolutionary constraints

The paper identifies reversion mutations in homologous recombination genes across cancers, showing they restore DNA repair and confer PARP inhibitor resistance through specific structural alterations.

Cooperative molecular interaction networks govern PARP1 inhibitor selectivity and binding affinity

The paper uses atomistic simulations to identify molecular interactions governing PARP1 inhibitor selectivity and binding affinity, revealing key residues and cooperative networks that influence inhibitor specificity.