ArticleOncotarget2016
Resistance to PARP inhibitors by SLFN11 inactivation can be overcome by ATR inhibition.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
191 citing papers in PubMed, 286 citations in OpenAlex.
- Phase II Randomized Study of Maintenance Atezolizumab Versus Atezolizumab Plus Talazoparib in Patients With SLFN11 Positive Extensive-Stage SCLC: S1929.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Trial
- A Dose-finding Study Followed by a Phase II Randomized, Placebo-controlled Trial of Chemoradiotherapy With or Without Veliparib in Stage III Non-small-cell Lung Cancer: SWOG 1206 (8811).Clinical lung cancer · 2021Trial
- Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, phase 2 trial.Lancet (London, England) · 2021Trial
- Randomized Phase II Trial of Cisplatin and Etoposide in Combination With Veliparib or Placebo for Extensive-Stage Small-Cell Lung Cancer: ECOG-ACRIN 2511 Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019Trial
- Randomized, Double-Blind, Phase II Study of Temozolomide in Combination With Either Veliparib or Placebo in Patients With Relapsed-Sensitive or Refractory Small-Cell Lung Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Safety and efficacy of ceralasertib, an ATR kinase inhibitor, combined with olaparib: dose escalation in advanced solid tumours and dose expansion in advanced breast cancer.British journal of cancer · 2026Article
- Histological heterogeneity of SLFN11 expression and its association with response to carboplatin plus paclitaxel therapy in salivary gland cancer.International journal of clinical oncology · 2026Article
- Molecular Determinants of Response and Rational Drug Combinations for Antibody-Drug Conjugates (ADCs) with Topoisomerase I (TOP1) Inhibitor Payloads.Journal of molecular biology · 2026Review
- Schlafen 11 Is Overexpressed in Multiple Myeloma and Undergoes Nucleolar Translocation in Response to Bortezomib.Cancer research communications · 2026Article
- Integrative analysis of SLFN11-related DEGs reveals novel biomarkers for cisplatin sensitivity and immune modulation in colorectal cancer.Cancer cell international · 2026Article
- Alkylating agents activate an SLFN11-dependent vulnerability that confers PARP-1 inhibitor sensitivity in kidney cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Mechanisms of PARP Inhibitor Resistance: From Replication Gap Biology and Transcription-Replication Conflicts to PROTAC-Based Next-Generation Strategies.Environmental and molecular mutagenesis · 2026Review
- BRCA1/2 Reversion Mutations in Japanese Patients with Metastatic Breast Cancer Progressing on Olaparib: OLIVE (WJOG15321B).Breast cancer (Tokyo, Japan) · 2026Observational
- Topoisomerase I inhibitor antibody-drug conjugates in breast cancer: the relevance of the DNA damage response to resistance, response, and combination treatment strategies.Breast cancer research and treatment · 2026Review
- PARP Inhibition in Prostate Cancer: Current Status, Resistance Mechanisms, and Clinical Challenges.Cells · 2026Review
- Defective biological networks associated with pseudogene-derived lncRNAs in cancer drug resistance: Promising prospects for their clinical targets in cancer therapy.Genes & diseases · 2026Review
- Schlafen 11 (SLFN11) overexpression and nucleolar localization in response to bortezomib in multiple myeloma.bioRxiv : the preprint server for biology · 2026Article
- Targeting glycerophospholipid biosynthesis overcomes chemoresistance driven by SLFN11 loss in Ewing sarcoma.Cell death & disease · 2026Article
- Integrative proteomics reveals MSH6 to modulate PARP inhibitor sensitivity in BRCA1/2-proficient ovarian cancer.PloS one · 2026Article
- Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.Clinical and translational medicine · 2026Review
131 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Poly(ADP-ribose) polymerase inhibitors (PARPIs) kill cancer cells by trapping PARP1 and PARP2. Talazoparib, the most potent PARPI inhibitor (PARPI), exhibits remarkable selectivity among the NCI-60 cancer cell lines beyond BRCA inactivation. Our genomic analyses reveal high correlation between response to talazoparib and Schlafen 11 (SLFN11) expression. Causality was established in four isogenic SLFN11-positive and -negative cell lines and extended to olaparib. Response to the talazoparib-temozolomide combination was also driven by SLFN11 and validated in 36 small cell lung cancer cell lines, and in xenograft models. Resistance in SLFN11-deficient cells was caused neither by impaired drug penetration nor by activation of homologous recombination. Rather, SLFN11 induced irreversible and lethal replication inhibition, which was independent of ATR-mediated S-phase checkpoint. The resistance to PARPIs by SLFN11 inactivation was overcome by ATR inhibition, mechanistically because SLFN11-deficient cells solely rely on ATR activation for their survival under PARPI treatment. Our study reveals that SLFN11 inactivation, which is common (~45%) in cancer cells, is a novel and dominant resistance determinant to PARPIs.
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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.