ArticleClinical cancer research : an official journal of the American Association for Cancer Research2023
Targeting Replication Stress and Chemotherapy Resistance with a Combination of Sacituzumab Govitecan and Berzosertib: A Phase I Clinical Trial.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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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
34 citing papers in PubMed, 35 citations in OpenAlex.
- Phase II study of olaparib plus durvalumab in EGFR-mutant NSCLC transformed to small cell lung cancer.The oncologist · 2026Trial
- Tumor-targeted top1 inhibitor delivery with optimized parp inhibition in advanced solid tumors: a phase i trial of gapped scheduling.Nature communications · 2025Trial
- Sensitizing tumor response to topoisomerase I antibody-drug conjugate by selective CDK7 inhibition.Science advances · 2026Article
- Synthetic lethality in cancer: mechanisms, therapeutic exploitation and clinical translation.Signal transduction and targeted therapy · 2026Review
- The next generation of antibody-drug conjugates.Nature medicine · 2026Review
- TROP2 promotes bone metastasis of colorectal cancer through interaction with the fibronectin-integrin axis.Cellular and molecular life sciences : CMLS · 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
- CellMiner cross-database (CellMinerCDB) version 2.2 for explorations of patient-derived cancer cell line pharmacogenomics.Nucleic acids research · 2026Article
- Pathway for the Development of ATR Inhibitors in Pediatric Malignancies: An ACCELERATE Multistakeholder Analysis.JCO precision oncology · 2026Review
- Current and emerging therapies targeting cell surface antigens and epigenetics in extensive stage small cell lung cancer: primer for clinicians.Therapeutic advances in medical oncology · 2026Review
- Strategic Combinations of Antibody-Drug Conjugates from 2023 to 2025: From Dual Therapies to Innovative ADC-Based Regimens.Pharmaceutics · 2025Review
- Review
- The evolving landscape of antibody-drug conjugates (ADCs) for treatment of prostate cancer.NPJ precision oncology · 2025Review
- Lamin A/C loss promotes R-loop-mediated genomic instability and poor survival in small-cell lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Polymerase theta inhibition impairs tumor growth and amplifies melphalan-induced DNA damage in multiple myeloma.Journal of translational medicine · 2025Article
- Injectable thermosensitive hydrogel co-loading with ATRi and doxorubicin for the treatment of triple-negative breast cancer.RSC advances · 2025Article
- Advancing therapeutics in small-cell lung cancer.Nature cancer · 2025Review
- ANP32E drives vulnerability to ATR inhibitors by inducing R-loops-dependent transcription replication conflicts in triple negative breast cancer.Nature communications · 2025Article
- Lamin A/C Deficiency Drives Genomic Instability and Poor Survival in Small-Cell Lung Cancer through Increased R-loop Accumulation.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
35 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeDespite promising preclinical studies, toxicities have precluded combinations of chemotherapy and DNA damage response (DDR) inhibitors. We hypothesized that tumor-targeted chemotherapy delivery might enable clinical translation of such combinations. PATIENTS AND
methodsIn a phase I trial, we combined sacituzumab govitecan, antibody-drug conjugate (ADC) that delivers topoisomerase-1 inhibitor SN-38 to tumors expressing Trop-2, with ataxia telangiectasia and Rad3-related (ATR) inhibitor berzosertib. Twelve patients were enrolled across three dose levels.
resultsTreatment was well tolerated, with improved safety over conventional chemotherapy-based combinations, allowing escalation to the highest dose. No dose-limiting toxicities or clinically relevant ≥grade 4 adverse events occurred. Tumor regressions were observed in 2 patients with neuroendocrine prostate cancer, and a patient with small cell lung cancer transformed from EGFR-mutant non-small cell lung cancer.
conclusionsADC-based delivery of cytotoxic payloads represents a new paradigm to increase efficacy of DDR inhibitors. See related commentary by Berg and Choudhury, p. 3557.
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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.