ArticleDisease models & mechanisms2016
Lurbinectedin induces depletion of tumor-associated macrophages, an essential component of its in vivo synergism with gemcitabine, in pancreatic adenocarcinoma mouse models.
Article in Disease models & mechanisms, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05876715 (LINNOVATE), which is not on this map. Cited by 29 papers.
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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.
LINNOVATE: A Phase 1/2 Study of Safety/Efficacy Using LURBINECTEDIN, Combined With IPILIMUMAB, and NIVOLUMAB for Advanced Soft Tissue Sarcomas
Who cites it
29 citing papers in PubMed, 28 citations in OpenAlex.
- Boswellic Acid Enhances Gemcitabine's Inhibition of Hypoxia-Driven Angiogenesis in Human Endometrial Cancer.Medicina (Kaunas, Lithuania) · 2025Article
- Review
- TREM-1 as a novel immunotherapeutic target to treat pancreatic ductal adenocarcinoma.Molecular therapy. Oncology · 2025Article
- Unveiling the Mechanism of Lurbinectedin's Action and Its Potential in Combination Therapies in Small Cell Lung Cancer.Molecular cancer therapeutics · 2025Review
- Tumor-associated macrophages (TAMs): Constructing an immunosuppressive microenvironment bridge for pancreatic ductal adenocarcinoma (PDAC).Cancer pathogenesis and therapy · 2025Review
- A glycogen derived from sea urchin-Frontiers in pharmacology · 2025Article
- The Role of Macrophages in Hepatocellular Carcinoma and Their Therapeutic Potential.International journal of molecular sciences · 2024Review
- Drug resistance and tumor immune microenvironment: An overview of current understandings (Review).International journal of oncology · 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
- Article
- Preclinical Synergistic Combination Therapy of Lurbinectedin with Irinotecan and 5-Fluorouracil in Pancreatic Cancer.Current oncology (Toronto, Ont.) · 2023Article
- Review
- Barriers and opportunities for gemcitabine in pancreatic cancer therapy.American journal of physiology. Cell physiology · 2023Review
- Immunosuppressive tumor-associated macrophages expressing interlukin-10 conferred poor prognosis and therapeutic vulnerability in patients with muscle-invasive bladder cancer.Journal for immunotherapy of cancer · 2022Article
- Macrophage and Neutrophil Interactions in the Pancreatic Tumor Microenvironment Drive the Pathogenesis of Pancreatic Cancer.Cancers · 2021Review
- Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma: Therapeutic Opportunities and Clinical Challenges.Cancers · 2021Review
- Tumor Associated Macrophages: Origin, Recruitment, Phenotypic Diversity, and Targeting.Frontiers in oncology · 2021Review
- Tumor-associated macrophages: Role in the pathological process of tumorigenesis and prospective therapeutic use (Review).Biomedical reports · 2020Review
- Specific Effects of Trabectedin and Lurbinectedin on Human Macrophage Function and Fate-Novel Insights.Cancers · 2020Article
- Lurbinectedin: First Approval.Drugs · 2020Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We explored whether the combination of lurbinectedin (PM01183) with the antimetabolite gemcitabine could result in a synergistic antitumor effect in pancreatic ductal adenocarcinoma (PDA) mouse models. We also studied the contribution of lurbinectedin to this synergism. This drug presents a dual pharmacological effect that contributes to its in vivo antitumor activity: (i) specific binding to DNA minor grooves, inhibiting active transcription and DNA repair; and (ii) specific depletion of tumor-associated macrophages (TAMs). We evaluated the in vivo antitumor activity of lurbinectedin and gemcitabine as single agents and in combination in SW-1990 and MIA PaCa-2 cell-line xenografts and in patient-derived PDA models (AVATAR). Lurbinectedin-gemcitabine combination induced a synergistic effect on both MIA PaCa-2 [combination index (CI)=0.66] and SW-1990 (CI=0.80) tumor xenografts. It also induced complete tumor remissions in four out of six patient-derived PDA xenografts. This synergism was associated with enhanced DNA damage (anti-γ-H2AX), cell cycle blockage, caspase-3 activation and apoptosis. In addition to the enhanced DNA damage, which is a consequence of the interaction of the two drugs with the DNA, lurbinectedin induced TAM depletion leading to cytidine deaminase (CDA) downregulation in PDA tumors. This effect could, in turn, induce an increase of gemcitabine-mediated DNA damage that was especially relevant in high-density TAM tumors. These results show that lurbinectedin can be used to develop 'molecularly targeted' combination strategies.
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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.