ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
TROP2 Is Associated with Primary Resistance to Immune Checkpoint Inhibition in Patients with Advanced Non-Small Cell Lung Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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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
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- The efficacy and safety of sacituzumab govitecan in the treatment of breast cancer: a systemic review and meta-analysis of emerging clinical data.Frontiers in immunology · 2025Pooled it
- A Phase II Evaluation of the Efficacy and Safety of Sacituzumab Govitecan in Patients with Recurrent Uterine Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Evaluation of Biomarkers for Sacituzumab Govitecan in Metastatic Non-Small Cell Lung Cancer: Insights From the EVOKE-01 Study.Cancer research communications · 2026Trial
- First-line sacituzumab tirumotecan with tagitanlimab in advanced non-small-cell lung cancer: a phase 2 trial.Nature medicine · 2025Trial
- Analysis of PD1, LAG3, TIGIT, and TIM3 expression in human lung adenocarcinoma reveals a 25-gene signature predicting immunotherapy response.Cell reports. Medicine · 2024Trial
- Antibody-drug conjugates in lung cancer: clinical development, therapeutic advances, and emerging challenges.Cancer chemotherapy and pharmacology · 2026Review
- Prognostic and therapeutic importance of TROP-2 and MUC-1 in non-small cell lung cancer: A systematic review and meta-analysis.Biomedical reports · 2026Article
- Tumor-associated calcium signal transducer 2 expression as a promising therapeutic target in esophageal squamous cell carcinoma: a combined the Cancer Genome Atlas and an institutional cohort.Esophagus : official journal of the Japan Esophageal Society · 2026Article
- Guiding the Application of Immunotherapy in Nonsmall Cell Lung Cancer: The Role of Biomarkers.Thoracic cancer · 2026Review
- Antibody drug conjugates in gynaecological cancers: navigating between opportunities and challenges.EClinicalMedicine · 2026Review
- ADC Target Profiling in NSCLC: Generalizable AI Separates TROP-2 and cMET Phenotypes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Patient-derived three-dimensional lung tumor models to evaluate response to therapy.NPJ precision oncology · 2026Article
- Pan-cancer multi-omic integration of Trop2 reveals biological determinants and translational implications for ADC therapy.NPJ precision oncology · 2026Article
- Targeting TROP-2 in treatment-resistant non-small cell lung cancer harboring theOncology letters · 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
- Carbonic anhydrase 9 as a circulating biomarker and therapeutic target in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab.Journal for immunotherapy of cancer · 2026Article
- TROP2/claudin program mediates immune exclusion to impede checkpoint blockade in breast cancer.Journal for immunotherapy of cancer · 2026Article
- Cellular landscape and diagnostic value of TROP2 in cerebrospinal fluid of lung adenocarcinoma leptomeningeal metastases.NPJ precision oncology · 2026Article
- TROP2 confers resistance to oxidative stress-induced cancer cell death through YAP/HMOX1 signaling.Journal of translational medicine · 2026Article
- Spatial heterogeneity of antibody-drug conjugate targets in pancreatic ductal adenocarcinoma.The journal of pathology. Clinical research · 2026Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeMechanisms of primary resistance to inhibitors of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling axis in non-small cell lung cancer (NSCLC) are still poorly understood. While some studies suggest the involvement of trophoblast cell surface antigen 2 (TROP2) in modulating tumor cell resistance to therapeutic drugs, its specific role in the context of PD-1/PD-L1 axis blockade is not definitively established. EXPERIMENTAL
designWe performed high-throughput analysis of transcriptomic data from 891 NSCLC tumors from patients treated with either the PD-L1 inhibitor atezolizumab or chemotherapy in two large randomized clinical trials. To confirm our results at the protein level, we complemented this transcriptional approach by performing a multiplex immunofluorescence analysis of tumor tissue samples as well as a proteomic profiling of plasma.
resultsWe observed a significant association of TROP2 overexpression with worse progression-free survival and overall survival on PD-L1 blockade, independent of other prognostic factors. Importantly, we found increased TROP2 expression to be predictive of survival in patients treated with atezolizumab but not chemotherapy. TROP2 overexpression was associated with decreased T-cell infiltration. We confirmed these results at the proteomic level both on tumor tissue and in plasma.
conclusionsOur results suggest an important contribution of TROP2 expression to the primary resistance to PD-L1 blockade in NSCLC. TROP2-biomarker-based strategy may be relevant in selecting patients with NSCLC who are more likely to benefit from a combination of immunotherapy and an anti-TROP2 agent.
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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.