ArticleGut2025
TPX2 serves as a novel target for expanding the utility of PARPi in pancreatic cancer through conferring synthetic lethality.
Article in Gut, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Organoids in translation: a bench-to-bedside framework for pancreatic cancer precision medicine.Journal of translational medicine · 2026Pooled it
- Evaluation of translational potential of mRNA vaccine candidate antigens for pancreatic cancer: a systematic review based on clinical evidence and stratified prioritization strategies.Frontiers in immunology · 2026Pooled it
- Kinesins in Cancer Drug Resistance: Mechanisms, Therapeutic Targeting, and Translational Potential.Cancers · 2026Review
- Single-cell and bulk transcriptomics identify senescence-related EMT transcriptional programs and a prognostic framework in pancreatic ductal adenocarcinoma.BMC gastroenterology · 2026Article
- Synthetic lethality in cancer: mechanism exploration and therapeutic applications.Cell communication and signaling : CCS · 2026Review
- Pancancer Fine-Mapping of Mutational Intolerance Identifies CHEK1 as an Immunosuppressive Driver in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DNA damage response inhibitors in pancreatic cancer: progress and challenges.Frontiers in oncology · 2026Review
- Article
- TPX2-mediated autophagy maintains cancer stemness in LUAD: bioinformatic screening and functional validation.Frontiers in oncology · 2026Article
- TPX2 promotes ferroptosis in LPS-induced C28/I2 chondrocytes via NF-κB p65-mediated downregulation of GPX4 and SLC7A11.Molecular biology reports · 2025Article
- Post-Translational Modifications: Key "Regulators" of Pancreatic Cancer Malignant Phenotype-Advances in Mechanisms and Targeted Therapies.Biomedicines · 2025Review
- Bibliometric analysis of global research trends in pancreatic cancer immunotherapy.Human vaccines & immunotherapeutics · 2025Article
- Review
- Prognostic Significance of Overexpression of BCL9 and TPX2 in High-Grade Clear Cell Renal Cell Carcinoma: Prognostic Markers for Metastasis and Survival.International journal of molecular sciences · 2025Article
- Identification of DNA damage and repair gene-related markers in pancreatic ductal adenocarcinoma by single-cell and bulk RNA sequencing.Discover oncology · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPARP inhibitors (PARPi) have been licensed for the maintenance therapy of patients with metastatic pancreatic cancer carrying pathogenic germline BRCA1/2 mutations. However, mutations in BRCA1/2 are notably rare in pancreatic cancer.
objectiveThere is a significant unmet clinical need to broaden the utility of PARPi.
designRNA sequencing was performed to screen potential targets for PARPi sensitivity. The synthetic lethal effects were verified in patient-derived xenograft (PDX), xenograft and patient-derived organoid models. Mechanisms were explored via LC‒MS/MS, coimmunoprecipitation, laser microirradiation, immunofluorescence, the homologous recombination (HR) or non-homologous end joining (NHEJ) reporter system, in situ proximity ligation assay and live-cell time-lapse imaging analyses.
resultsTargeting protein for Xenopus kinesin-like protein 2 (TPX2) is an exploitable vulnerability. TPX2 was downregulated in PDX models sensitive to PARPi, and TPX2 inhibition conferred synthetic lethality to PARPi both
conclusionsOur findings revealed the dual-functional significance of TPX2 in controlling DNA DSB repair pathway choice and mitotic progression, suggesting a potential therapeutic strategy involving PARPi for patients with pancreatic cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.