PARP inhibition in cancer therapy

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.

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.

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.

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.

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.

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.

Multimodal imaging reveals a lysosomal drug reservoir that drives heterogeneous distribution of PARP inhibitors

The paper uses multimodal imaging to show that lysosomes act as a reservoir for PARP inhibitors, leading to heterogeneous drug distribution and response in ovarian cancer.

Lack of synergy between AR targeted therapies and PARP inhibitors in homologous recombination-proficient prostate cancer

This study shows that AR inhibition does not enhance PARP inhibitor efficacy in HR-proficient prostate cancer and instead impairs response in castration-sensitive cells.

An inducible BRCA1 expression system with in vivo applicability uncovers activity of the combination of ATR and PARP inhibitors to overcome therapy resistance

This paper develops an inducible BRCA1 expression system to study hypomorphic variants and finds that combining ATR and PARP inhibitors overcomes resistance caused by BRCA1 {Delta}exon11 hypomorphs.

Assessing PARP trapping dynamics in ovarian cancer using a CRISPR-engineered FRET biosensor

This paper develops a CRISPR-engineered FRET biosensor to study PARP trapping dynamics in ovarian cancer cells and identifies reduced trapping in PARPi-resistant models.

RAS/PI3K pathway mutations sensitise epithelial ovarian cancer cells to a PARP/NAMPT inhibitor combination

This study identifies RAS/PI3K pathway mutations as a biomarker for sensitivity to PARP/NAMPT inhibitor combination therapy in epithelial ovarian cancer.

Loss-of-Function genetic Screen Unveils Synergistic Efficacy of PARG Inhibition with Combined 5-Fluorouracil and Irinotecan Treatment in Colorectal Cancer

This study identifies PARG as a therapeutic target in colorectal cancer, showing that its inhibition synergizes with 5FU and irinotecan to improve treatment efficacy.

Long-term patient-derived ovarian cancer organoids closely recapitulate tumor of origin and clinical response

This study establishes patient-derived ovarian cancer organoids that mimic tumor characteristics and drug responses, showing potential for precision medicine.

Androgen receptor inhibition extends PARP inhibitor activity in prostate cancer models beyond BRCA mutations and defects in homologous recombination repair.

This study shows that combining androgen receptor inhibitors with PARP inhibitors enhances DNA damage in prostate cancer models, independent of BRCA mutations, by increasing double-strand breaks and micronuclei formation.

PARP inhibitors elicit distinct transcriptional programs in homologous recombination competent castration-resistant prostate cancer

This study examines how PARP inhibitors affect transcriptional responses in prostate cancer patients of different racial backgrounds, finding race-based differences in PARP1 expression and distinct transcriptional programs for each inhibitor.

Unmatched cell line collections are not optimal for identification of PARP inhibitor response and drug synergies

This study shows that unmatched cell line collections are not reliable for identifying PARP inhibitor response and synergies, and suggests isogenic models are more accurate.

An organoid platform reveals MEK-PARP co-targeting to enhance radiation response in rectal cancer

The paper uses a patient-derived rectal cancer organoid platform to identify MEK and PARP inhibitors that synergize with radiation to enhance treatment response in locally advanced rectal cancer.

Effects of a Cancer-Associated Mutation and Multiple SerinePhosphorylation on Poly(ADP-Ribose) Polymerase 2

This paper investigates how a cancer-associated mutation and serine phosphorylation affect the structure and function of PARP2, showing that PTMs can mitigate the mutation's structural impact.

PARP inhibition enhances exemestane efficacy in triple-negative breast cancer

This study identifies Exemestane as a synergistic partner for Olaparib in triple-negative breast cancer, enhancing efficacy through DNA damage and apoptosis.

5hmC enhances PARP trapping and restores PARP inhibitor sensitivity in chemoresistant BRCA1/2-deficient cells

This study shows that 5hmC increases PARP1 trapping on chromatin in olaparib-treated cells, restoring PARP inhibitor sensitivity in BRCA1/2-deficient cancer cells.

DNA polymerase beta expression in head & neck cancer modulates the poly(ADP-ribose)-mediated replication checkpoint

This study shows that DNA polymerase beta modulates the PARG-mediated replication checkpoint in HNSCC, and combining PARG and ATR/CHK1 inhibitors overcomes resistance.

Sequential ATR and PARP Inhibition Overcomes Acquired DNA Damaging Agent Resistance in Pancreatic Ductal Adenocarcinoma

This study shows that sequential ATR and PARP inhibition can overcome acquired resistance to DNA damaging agents in pancreatic ductal adenocarcinoma.

Replication stress marker phospho-RPA2 predicts response to platinum and PARP inhibitors in homologous recombination-proficient ovarian cancer

This study identifies phospho-RPA2 as a biomarker predicting response to platinum and PARP inhibitors in HR-proficient ovarian cancer, showing higher pathologic complete response and longer survival in pRPA2-High tumors.

H3K27M diffuse midline glioma is homologous recombination defective and sensitized to radiotherapy and NK cell-mediated antitumor immunity by PARP inhibition

This study shows H3K27M diffuse midline glioma is HRR defective and radiosensitized by PARP inhibitors, with enhanced NK cell-mediated immunity.

Targeting FEN1 to enhance efficacy of PARP inhibition in triple-negative breast cancer

This study identifies FEN1 as a target to enhance PARP inhibitor efficacy in PARPi-resistant triple-negative breast cancer cell lines and organoids.

Duplexed CeTEAM drug biosensors reveal determinants of PARP inhibitor selectivity

This study uses CeTEAM biosensors to profile PARP inhibitor selectivity at the single-cell level, revealing PARP1 and PARP2 selectivity patterns and the role of HPF1 in drug binding.

SETD1A-dependent EME1 transcription drives PARPi sensitivity in HR deficient tumour cells

This study shows that SETD1A promotes PARPi sensitivity in HR-deficient tumor cells by regulating EME1 transcription, and its loss leads to resistance.

Impact of a Cancer-Associated Mutation on Poly(ADP-ribose) Polymerase1 Inhibition

This study examines how the V762A PARP1 mutation affects binding of three PARP inhibitors, finding that talazoparib binds more effectively to the mutant and alters its dynamics differently than the wild-type.