ReviewClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2026
Reprogramming resistance in advanced lung cancer: epigenetic modulation to restore therapeutic vulnerability.
Review in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
1 citing paper in PubMed.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer is the most prevalent cancer and cause of death; most patients present themselves at an advanced stage and continuously acquire resistance to targeted agents, antibody-drug conjugates, chemotherapy, and immune checkpoint inhibitors. In addition to secondary mutations, epigenetically driven cellular plasticity, including DNA methylation, histone modification, chromatin remodeling, RNA (m 6A)-marks, and non-coding RNAs, facilitates resistance coordination, EMT/drug-tolerant persisters, lineage switching (e.g., NSCLC to NSCLC), bypass signaling, and immune evasion by tumor cells. These states can be therapeutically rewired by epigenetic drugs: low-dose DNMT/HDAC priming restores silenced tumor-suppressor and antigen-presentation genes and activates viral-mimicry interferon signaling to augment checkpoint blockade; EZH2 and LSD1 inhibitors target plasticity and neuroendocrine programs; BET inhibition suppresses adaptive transcription; CBP/p300 modulators suppress NRF2-dependent redox survival; Combination therapies exploiting synthetic lethality through PRMT5 inhibition, applied rationally with TKIs, ICIs, chemotherapy, and antibody-drug conjugates (ADCs), are currently under clinical investigation. Biomarker-directed patient selection (e.g., MTAP loss clustering, EZH2/LSD1 activity, methylation and chromatin signatures, and liquid biopsy dynamics of methylation or ctDNA) will be critical to enrich for patients most likely to benefit. In the future, better optimized sequencing using short priming windows, intermittent dosing, and future readouts of prospective pharmacodynamics could transform transient re-sensitization into lasting control. This study aims to critically appraise mechanistic and clinical evidence linking epigenetic plasticity to therapy resistance in advanced lung cancer and to propose biomarker-directed epigenetic combination and sequencing strategies to restore drug sensitivity.
Indexed as
Identifiers
41866608What Socratic holds
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.