ArticleCell death & disease2022
Osimertinib and anti-HER3 combination therapy engages immune dependent tumor toxicity via STING activation in trans.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Mitochondrial mechanisms underlying spatial immune phenotypes in non‑small cell lung cancer: Implications for ICI response and cold‑to‑hot tumor conversion (Review).Oncology reports · 2026Review
- PARP inhibition enhances the antitumor activity of HER3-DXd in non-small cell lung cancer.Cell reports. Medicine · 2026Article
- A combined strategy of EGFR-MET bispecific antibody and HER3 ADC to overcome osimertinib resistance in NSCLC.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Risk factors for radiation pneumonitis in NSCLC patients treated with third-generation EGFR TKIs and chest radiotherapy.Radiation oncology (London, England) · 2025Article
- Emerging importance of HER3 in tumorigenesis and cancer therapy.Nature reviews. Clinical oncology · 2025Review
- Integrating network pharmacology and experimental validation to explore the potential mechanism by which resveratrol acts on osimertinib resistance in lung cancer.Oncology letters · 2025Article
- Article
- Optimizing Osimertinib for NSCLC: Targeting Resistance and Exploring Combination Therapeutics.Cancers · 2025Review
- Griffithazanone A, a sensitizer of EGFR-targeted drug inHeliyon · 2024Article
- Combined therapy of dabrafenib and an anti-HER2 antibody-drug conjugate for advanced BRAF-mutant melanoma.Cellular & molecular biology letters · 2024Article
- Role of STING in the treatment of non-small cell lung cancer.Cell communication and signaling : CCS · 2024Review
- Bidirectional regulation of the cGAS-STING pathway in the immunosuppressive tumor microenvironment and its association with immunotherapy.Frontiers in immunology · 2024Review
- The cGAS-STING pathway: a therapeutic target in diabetes and its complications.Burns & trauma · 2024Review
- The proto-oncogene SRC phosphorylates cGAS to inhibit an antitumor immune response.JCI insight · 2023Article
- Label-free nanoscale mapping of intracellular organelle chemistry.Communications biology · 2023Article
- HER3-targeted therapeutic antibodies and antibody-drug conjugates in non-small cell lung cancer refractory to EGFR-tyrosine kinase inhibitors.Chinese medical journal pulmonary and critical care medicine · 2023Review
- Review
- Tumor-associated macrophages mediate resistance of EGFR-TKIs in non-small cell lung cancer: mechanisms and prospects.Frontiers in immunology · 2023Review
- Changes of tumor microenvironment in non-small cell lung cancer after TKI treatments.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
40 authors at 7 institutions in 3 countries.
Funding
Abstract
Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TKI) osimertinib. This new drug extends lifespan by 9-months vs. second-generation TKIs, but unfortunately, cancers relapse due to resistance mechanisms and the lack of antitumor immune responses. Here we explored the combination of osimertinib with anti-HER3 monoclonal antibodies and observed that the immune system contributed to eliminate tumor cells in mice and co-culture experiments using bone marrow-derived macrophages and human PBMCs. Osimertinib led to apoptosis of tumors but simultaneously, it triggered inositol-requiring-enzyme (IRE1α)-dependent HER3 upregulation, increased macrophage infiltration, and activated cGAS in cancer cells to produce cGAMP (detected by a lentivirally transduced STING activity biosensor), transactivating STING in macrophages. We sought to target osimertinib-induced HER3 upregulation with monoclonal antibodies, which engaged Fc receptor-dependent tumor elimination by macrophages, and STING agonists enhanced macrophage-mediated tumor elimination further. Thus, by engaging a tumor non-autonomous mechanism involving cGAS-STING and innate immunity, the combination of osimertinib and anti-HER3 antibodies could improve the limited therapeutic and stratification options for advanced stage lung cancer patients with mutant EGFR.
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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.