ReviewFrontiers in oncology2025
Pharmacological strategies to overcome immune checkpoint inhibitor resistance in non-small cell lung cancer.
Review in Frontiers in oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- From Mechanisms to Therapeutic Innovation in Non-Small Cell Lung Cancer: A Knowledge-Depth Translational Mapping with Experimental Validation.International journal of molecular sciences · 2026Article
- The tumor microenvironment: a dynamic ecosystem and therapeutic nexus in modern oncology.Frontiers in pharmacology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint inhibitors (ICIs) have redefined the therapeutic paradigm of non-small cell lung cancer (NSCLC), offering durable remission in select patients by reactivating anti-tumor T cell responses. Yet, this clinical triumph is tempered by the reality that most patients experience either primary resistance or relapse due to acquired resistance, underscoring an urgent need for mechanistically grounded solutions. Resistance arises through a complex interplay of tumor-intrinsic mechanisms, including defects in antigen presentation, interferon signaling disruption, and oncogenic pathway activation (EGFR, KRAS, MET), and tumor-extrinsic factors such as immunosuppressive cell populations, inhibitory cytokines, and metabolic rewiring of the tumor microenvironment (TME). This review provides a comprehensive synthesis of emerging pharmacological strategies aimed at reversing ICI resistance in NSCLC. Promising avenues include dual or multi-checkpoint inhibition (targeting LAG-3, TIGIT, TIM-3), integration of epigenetic reprogrammers to resensitize immune-silent tumors, and metabolic interventions that normalize the TME. Additionally, combination regimens with oncogene-directed therapies, engineered cytokine analogs, neoantigen-based vaccines, and adoptive T cell therapies are reshaping the frontier of immunoresistant NSCLC management. We also highlight pivotal clinical trials-both completed and ongoing that illuminate translational breakthroughs and therapeutic pitfalls. Looking ahead, the field must grapple with key challenges: the refinement of predictive biomarkers, stratification of patients through genomic, immunologic, and microbiome-based profiling, and the management of toxicity in complex combination protocols. Ultimately, a shift toward highly personalized, biomarker-guided therapeutic strategies holds the greatest promise for overcoming resistance and extending the reach of immunotherapy in NSCLC.
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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 Socratic graph.