ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
Multidimensional Analysis of B7 Homolog 3 RNA Expression in Small Cell Lung Cancer Molecular Subtypes.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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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
18 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Efficacy and safety of B7-H3-targeted antibody-drug conjugates in previously treated small cell lung cancer: a systematic review and meta-analysis with a contextual comparison to topotecan.Frontiers in immunology · 2026Pooled it
- Antibody-drug conjugates in advanced small-cell lung cancer: a systematic review and single-arm meta-analysis of later-line monotherapy.Frontiers in immunology · 2026Pooled it
- Review
- Decoding Small Cell Lung Cancer: Molecular Subtypes, Surface Antigens, and the Target-Modality Problem.Cancers · 2026Review
- Research progress on immune microenvironment and biomarkers of small cell lung cancer.Journal of thoracic disease · 2026Review
- Small Cell Lung Cancer Classification: Unraveling Heterogeneity to Enable Personalized Treatments.Cancer research · 2026Review
- Updates on Antibody Drug Conjugates and Bispecific T-Cell Engagers in SCLC.Antibodies (Basel, Switzerland) · 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
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- Clinical utility of molecular profiling in rare lung neuroendocrine neoplasms.Frontiers in oncology · 2026Review
- Seizure-Related Homolog Protein 6 (SEZ6): Biology and Therapeutic Target in Neuroendocrine Carcinomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- IDeate-Lung02: a Phase 3 study of second-line ifinatamab deruxtecan in patients with relapsed small cell lung cancer.Future oncology (London, England) · 2025Article
- Sacituzumab govitecan: another emerging treatment option for patients with relapsed small cell lung cancer.Translational lung cancer research · 2025Article
- Small cell lung cancer (SCLC): At the door of targeted therapies.Biomolecules & biomedicine · 2025Article
- ADCs and TCE in SCLC Therapy: The Beginning of a New Era?Current oncology (Toronto, Ont.) · 2025Review
- Frontiers in thoracic oncology: new breakthroughs in molecular targets and immunotherapy.Frontiers in immunology · 2025Review
- Antibody-Based Therapeutics in Small Cell Lung Cancer: A Narrative Review.Biologics : targets & therapy · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
purposeB7 homolog 3 (B7-H3) is a promising target for antibody-drug conjugates, with ifinatamab deruxtecan demonstrating an objective response rate of 54.8% in previously treated extensive-stage small cell lung cancer (SCLC). This analysis aimed to characterize B7-H3 RNA expression with reference to SCLC molecular subtypes (SCLC-A, SCLC-N, SCLC-P, and SCLC-I) and immune-related parameters. EXPERIMENTAL
designTumor RNA expression and mutational burden for 1,721 patients with SCLC were derived from a real-world database (Caris Life Sciences). A predominant molecular subtype was assigned based on RNA expression using a gene-ratio classifier. PD-L1 expression was assessed by IHC (antibody 22C3; positive cutoff: tumor proportion score ≥1%).
resultsThe predominant molecular subtype was SCLC-A in 848 (49.3%), SCLC-N in 202 (11.7%), SCLC-P in 142 (8.3%), SCLC-I in 291 (16.9%), and equivocal in 238 (13.8%) samples. B7-H3 expression was high and consistent among subtypes (q > 0.05), whereas DLL3 and SEZ6 expression each differed significantly (both q < 0.0001). PD-L1 positivity was similar across B7-H3 expression quartiles (range, 39.2%-46.5%). Median (95% confidence interval) B7-H3 expression was comparable between patients with and without prior immunotherapy [18.7 (16.5-21.2) and 17.3 (16.4-18.1) transcripts per million, respectively]. B7-H3 was not correlated with a T-cell signature but showed a strong correlation with HAVCR2/TIM3, CD86, PDCD1LG2/PD-L2, and M2 macrophages.
conclusionsB7-H3 showed consistent, high expression across SCLC molecular subtypes, whereas DLL3 and SEZ6 expression varied significantly. These data suggest that B7-H3-targeting antibody-drug conjugates may be active across SCLC subtypes, consistent with the high reported response rates.
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