ArticleEMBO molecular medicine2023
ATR inhibition augments the efficacy of lurbinectedin in small-cell lung cancer.
Article in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04802174 (A Phase I/II Trial of Lurbinectedin With Berzosertib, an ATR Kinase Inhibitor in Small Cell Cancers and High Grade Neuroendocrine Cancers), which is not on this map. Cited by 21 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.
A Phase I/II Trial of Lurbinectedin With Berzosertib, an ATR Kinase Inhibitor in Small Cell Cancers and High Grade Neuroendocrine Cancers
Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Trial
- Article
- Spatial multi-omics unveils the monoclonal origin, neuroendocrine plasticity, and microenvironment niches in combined small-cell lung cancer.Cell reports. Medicine · 2026Article
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- Lineage plasticity and histological transformation: tumor histology as a spectrum.Cell research · 2025Review
- The Effect of Lurbinectedin as a Monotherapy and in Combination with Ionizing Radiation on Sarcoma Cell Lines.Cancers · 2025Article
- ATR expression as a prognostic biomarker inJournal of thoracic disease · 2025Article
- Current landscape of innovative drug development and regulatory support in China.Signal transduction and targeted therapy · 2025Review
- Unveiling the Mechanism of Lurbinectedin's Action and Its Potential in Combination Therapies in Small Cell Lung Cancer.Molecular cancer therapeutics · 2025Review
- Advancing therapeutics in small-cell lung cancer.Nature cancer · 2025Review
- The dual HDAC/PI3K inhibitor CUDC-907 inhibits the growth and proliferation of MYC-driven Group 3 medulloblastoma.Cell death discovery · 2025Article
- Review
- Asia-inclusive drug development leveraging principles of ICH E5 and E17 guidelines: Case studies illustrating quantitative clinical pharmacology as a foundational enabler.Clinical and translational science · 2024Review
- GCN2 is a determinant of the response to WEE1 kinase inhibition in small-cell lung cancer.Cell reports · 2024Article
- Small cell lung cancer: emerging subtypes, signaling pathways, and therapeutic vulnerabilities.Experimental hematology & oncology · 2024Review
- Microenvironment shapes small-cell lung cancer neuroendocrine states and presents therapeutic opportunities.Cell reports. Medicine · 2024Article
- Small cells - big issues: biological implications and preclinical advancements in small cell lung cancer.Molecular cancer · 2024Review
- P53 and Rb Aberrations in Small Cell Lung Cancer (SCLC): From Molecular Mechanisms to Therapeutic Modulation.International journal of molecular sciences · 2024Review
- Trabectedin and Lurbinectedin Modulate the Interplay between Cells in the Tumour Microenvironment-Progresses in Their Use in Combined Cancer Therapy.Molecules (Basel, Switzerland) · 2024Review
- Actionable Driver Events in Small Cell Lung Cancer.International journal of molecular sciences · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
26 authors at 4 institutions in 5 countries.
Funding
Abstract
Small-cell lung cancer (SCLC) is the most lethal type of lung cancer. Specifically, MYC-driven non-neuroendocrine SCLC is particularly resistant to standard therapies. Lurbinectedin was recently approved for the treatment of relapsed SCLC, but combinatorial approaches are needed to increase the depth and duration of responses to lurbinectedin. Using high-throughput screens, we found inhibitors of ataxia telangiectasia mutated and rad3 related (ATR) as the most effective agents for augmenting lurbinectedin efficacy. First-in-class ATR inhibitor berzosertib synergized with lurbinectedin in multiple SCLC cell lines, organoid, and in vivo models. Mechanistically, ATR inhibition abrogated S-phase arrest induced by lurbinectedin and forced cell cycle progression causing mitotic catastrophe and cell death. High CDKN1A/p21 expression was associated with decreased synergy due to G1 arrest, while increased levels of ERCC5/XPG were predictive of increased combination efficacy. Importantly, MYC-driven non-neuroendocrine tumors which are resistant to first-line therapies show reduced CDKN1A/p21 expression and increased ERCC5/XPG indicating they are primed for response to lurbinectedin-berzosertib combination. The combination is being assessed in a clinical trial NCT04802174.
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Identifiers
What OpenQuestion holds
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.