ArticleCancer discovery2026
Circulating Tumor Cells Predict Response to the DLL3-Targeting Bispecific Antibody Tarlatamab.
Article in Cancer discovery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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
14 citing papers in PubMed.
- Towards liquid biopsy-based analysis of antitumour immunity.Nature reviews. Clinical oncology · 2026Review
- Consolidated Evidence and New Frontiers of Liquid Biopsy in Lung Cancer: A Narrative Review.Cells · 2026Review
- Integrating molecular subtypes, genomics and functional dependencies to identify context-specific therapeutic vulnerabilities in small cell lung cancer.Biomarker research · 2026Review
- Liquid biopsy in solid tumours: expert opinion paper of the European society of pathology.Virchows Archiv : an international journal of pathology · 2026Review
- T-Cell Engagers in Lung Cancer: A Comprehensive Literature Review from Tarlatamab Approval to Next-Generation Strategies.Cancers · 2026Review
- Dynamic monitoring of antibody drug conjugates targeting TROP2 or HER2 in breast cancer using circulating tumor cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- IAR025, a novel anti-DLL3 x CD3-bispecific antibody, displays high antitumor efficacy in preclinical models of small-cell lung cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Transcription Factor Subtype Governs Response and Resistance to DLL3-Directed T-Cell Engagement in Small Cell Lung Cancer.bioRxiv : the preprint server for biology · 2026Article
- DLL3-directed immune redirection in small-cell lung cancer: a lineage-defined vulnerability that doubles as an escape route.Frontiers in immunology · 2026Review
- Bispecific antibodies in gastrointestinal cancers: current applications and future perspectives.Frontiers in oncology · 2026Review
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- Reframing small cell lung cancer: therapeutic lessons from hematologic malignancies.Frontiers in 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
- Liquid biopsies for detection, characterization, and interception of therapy resistance in thoracic malignancies.Frontiers in oncology · 2026Review
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
The bispecific antibody tarlatamab recruits T cells to cancers expressing the neuroendocrine epitope delta-like ligand 3 (DLL3). Tarlatamab is effective in small cell lung cancer (SCLC), but clinical outcomes vary, and no biomarkers enable patient selection. Single-cell RNA sequencing of SCLC biopsies identifies heterogeneity in DLL3 expression, and analysis of circulating tumor cells (CTC) distinguishes individual patients as predominantly DLL3Pos or DLL3Low. In a prospective cohort of 20 patients, pretreatment DLL3 expression on CTCs predicts tarlatamab clinical benefit (85% sensitivity and 100% specificity). Necrotic CTC clusters in blood accompany treatment-induced tumor lysis. Acquired resistance to tarlatamab is associated in some cases with loss of DLL3 expression but persistence of other targetable neuroendocrine epitopes; in other patients, DLL3 is retained on CTCs but accompanied by systemic markers of T-cell dysfunction. Quantitation of DLL3-positive CTCs identifies patients likely to benefit from tarlatamab, and longitudinal monitoring may guide therapeutic decision-making at the time of acquired resistance. SIGNIFICANCE: CTCs are abundant in SCLC, allowing noninvasive quantitation of epitopes targeted by immune therapies. Patients with at least 25% DLL3-positive CTCs derive clinical benefit from a bispecific antibody targeting this epitope; those with a lower fraction rarely respond. CTC scoring may thus enable stratification of patients for antibody-mediated therapeutics.
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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.