ArticleScience translational medicine2020
BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers.
Article in Science translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 137 citations in OpenAlex.
- Olaparib monotherapy or combination therapy in lung cancer: an updated systematic review and meta- analysis.Frontiers in oncology · 2025Pooled it
- 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
- Tumor-on-chip as a personalized platform for rapid drug testing in breast cancer.Cell reports. Medicine · 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
- Replication origin flexibility: a tool to mitigate the hazards of excess replication.Trends in genetics : TIG · 2026Review
- Loss of Payload Sensitivity and Other Mechanisms of Resistance to T-DXd in HER2-Mutant NSCLC: Implications for Subsequent Responsiveness to HER2 TKIs.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Antibody-drug conjugates in breast cancer: Progress and future directions.Cell reports. Medicine · 2026Review
- Targeting PRMTs Creates Vulnerability of DNA Double-Stand Break Repair Pathways, and Potentiates Chemotherapy Efficacy in TNBC.Cancer science · 2026Article
- From biology to the clinic: research evidence and therapeutic advances of TROP2-targeted antibody-drug conjugates in small cell lung cancer.Translational lung cancer research · 2026Review
- 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
- Ubiquitin-dependent recruitment of SLFN11 to chromatin is regulated by deubiquitinase (DUB) and RNF168.Research square · 2026Article
- DNA Damage and Nuclear Anaplasia Induced by Trastuzumab Deruxtecan in Cancer Cells with Variable HER2 Expression and Homologous Recombination Deficiency Status.Cancer research and treatment · 2026Article
- Dual targeting of topoisomerase I and DNA G-quadruplexes enhances senescence and chemosensitivity in colorectal cancer.Communications biology · 2026Article
- Advances in Targeting HER2 across Cancer Subtypes: A Pan-Tumor Approach.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Post-translational modifications in retinoblastoma: mechanisms, immune regulation, and therapeutic opportunities.Frontiers in immunology · 2026Review
- A comprehensive analysis of humanized mouse models for the study of cancer immunotherapies.Frontiers in immunology · 2026Article
- Impact of GermlineOncology research · 2026Article
- Derivation of AZD5335, a Novel FRα-Targeted TOP1i-Loaded ADC, for the Treatment of FRα-Expressing Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Mechanisms of resistance to antibody-drug conjugates in cancer: molecular barriers and pharmacological solutions.Cancer chemotherapy and pharmacology · 2025Review
- Co-expression of CD30 and SLFN11 serves as a dual biomarker for the treatment of cutaneous T-cell lymphoma.NAR cancer · 2025Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
34 authors at 8 institutions in 5 countries.
Funding
Abstract
Topoisomerase I (TOP1) inhibitors trap TOP1 cleavage complexes resulting in DNA double-strand breaks (DSBs) during replication, which are repaired by homologous recombination (HR). Triple-negative breast cancer (TNBC) could be eligible for TOP1 inhibitors given the considerable proportion of tumors with a defect in HR-mediated repair (BRCAness). The TOP1 inhibitor irinotecan was tested in 40 patient-derived xenografts (PDXs) of TNBC. BRCAness was determined with a single-nucleotide polymorphism (SNP) assay, and expression of Schlafen family member 11 (SLFN11) and retinoblastoma transcriptional corepressor 1 (RB1) was evaluated by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry analyses. In addition, the combination of irinotecan and the ataxia telangiectasia and Rad3-related protein (ATR) inhibitor VE-822 was tested in SLFN11-negative PDXs, and two clinical non-camptothecin TOP1 inhibitors (LMP400 and LMP776) were tested. Thirty-eight percent of the TNBC models responded to irinotecan. BRCAness combined with high SLFN11 expression and RB1 loss identified highly sensitive tumors, consistent with the notion that deficiencies in cell cycle checkpoints and DNA repair result in high sensitivity to TOP1 inhibitors. Treatment by the ATR inhibitor VE-822 increased sensitivity to irinotecan in SLFN11-negative PDXs and abolished irinotecan-induced phosphorylation of checkpoint kinase 1 (CHK1). LMP400 (indotecan) and LMP776 (indimitecan) showed high antitumor activity in BRCA1-mutated or BRCAness-positive PDXs. Last, low SLFN11 expression was associated with poor survival in 250 patients with TNBC treated with anthracycline-based chemotherapy. In conclusion, a substantial proportion of TNBC respond to irinotecan. BRCAness, high SLFN11 expression, and RB1 loss are highly predictive of response to irinotecan and the clinical indenoisoquinoline TOP1 inhibitors.
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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.