EGFR‐mutated stage IV non‐small cell lung cancer: What is the role of radiotherapy combined with TKI?

Liu, Bailong; Liu, Hui; Ma, You-Zhi; Ding, Qiuhui; Zhang, Min; Liu, Xinliang; Liu, Min

doi:10.1002/cam4.4192

Cited by 10 publications

(10 citation statements)

References 110 publications

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“…Among different subtypes, non-small cell lung carcinoma (NSCLC) is dominant at $85% of total cases and more than half of them diagnosed at advanced stages [2]. Surgery, chemotherapy, immunotherapy, and targeted therapy (such as anaplastic lymphoma kinase [ALK] tyrosine kinase inhibitors and epidermal growth factor receptor [EGFR]) are standard first and second line treatments provided for these patients and show good initial response and better survival outcomes for NSCLC patients [3]. Anlotinib is approved for use on patients with refractory NSCLC as a third line treatment option, given its significant benefits in progression free-and overall-survival [4,5].…”

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confidence: 99%

MNK/eIF4E inhibition overcomes anlotinib resistance in non‐small cell lung cancer

Zhang

et al. 2022

Fundamemntal Clinical Pharma

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Anlotinib is approved for refractory cases in advanced non‐small‐cell lung cancer (NSCLC). This is a novel oral multitarget tyrosine kinase inhibitor, but patients inevitably face prospects of drug resistance during the treatment process. Using anlotinib‐resistant NSCLC models, this work investigated the underlying molecular mechanism and systematically addressed the issue of anlotinib resistance. We demonstrated that expression and activity of eukaryotic translation initiation factor 4E (eIF4E) were upregulated in NSCLC cells due to prolonged exposure to anlotinib. eIF4E depletion resulted in significant effects to anlotinib‐resistant cells, showing proliferation inhibition and apoptosis inducement. We further showed that MAP kinase interacting serine/threonine kinase (MNK)‐dependent eIF4E inhibition by cercosporamide was active against anlotinib‐resistant cells and significantly augmented anlotinib's efficacy in parental NSCLC cells. Importantly, observations from in‐vitro experiments are consistent in in vivo anlotinib‐resistant and anlotinib‐sensitive NSCLC cancer xenograft mouse models. Our work is the first to reveal that eIF4E is involved intimately in anlotinib resistance development in NSCLC, and this eIF4E activation can be reversed by cercosporamide or other MNK inhibitors.

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confidence: 99%

MNK/eIF4E inhibition overcomes anlotinib resistance in non‐small cell lung cancer

Zhang

et al. 2022

Fundamemntal Clinical Pharma

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“… 28 , 29 Emerging evidence suggests that radiotherapy for metastatic lesions can improve the outcome in patients with advanced EGFR-mutant NSCLC. 15 , 30 , 31 Moreover, several studies have examined the activity of thoracic radiation in advanced NSCLC patients harboring TKI-sensitive EGFR mutations. 22 , 23 , 32 , 33 Zheng et al conducted a prospective study to assess the efficacy of thoracic radiotherapy in combination with EGFR-TKIs on stage IV EGFR mutant lung adenocarcinomas.…”

Section: Discussionmentioning

confidence: 99%

Survival benefit of thoracic radiotherapy plus EGFR-TKIs in patients with non-oligometastatic advanced non-small-cell lung cancer: a single-center retrospective study

et al. 2023

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Objectives: The study aims to evaluate the efficacy and safety of thoracic radiotherapy in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-treated patients with stage IV non-small-cell lung cancer (NSCLC). Methods: Patients with non-oligometastatic NSCLC harboring EGFR mutations were recruited. All patients received the first-generation TKI treatment with or without radiotherapy. The irradiated sites included primary and/or metastatic lesions. Of all the patients who underwent thoracic radiotherapy, some received radiotherapy before EGFR-TKI resistance, others received radiotherapy after progressive disease. Results: No statistically significant difference was observed in progression-free survival (PFS) (median 14.7 versus 11.2 months, p = 0.075) or overall survival (OS) (median 29.6 versus 40.6 months, p = 0.116) between patients treated with EGFR-TKIs alone and those with additional radiotherapy to any sites. However, EGFR inhibitors with thoracic radiation significantly improved OS (median 47.0 versus 31.0 months, p < 0.001) but not PFS (median 13.9 versus 11.9 months, p = 0.124). Moreover, longer PFS (median 18.3 versus 8.5 months, p < 0.001) was achieved in the preemptive thoracic radiation cohort than in the delayed thoracic radiation cohort. However, OS was similar between the two cohorts (median 40.6 versus 52.6 months, p = 0.124). The lower incidence rate of grade 1–2 pneumonitis occurred in preemptive radiation cohort (29.8% versus 75.8%, p < 0.001). Conclusion: Non-oligometastatic NSCLC patients with EGFR mutations benefited from thoracic radiotherapy while using EGFR inhibitors. Preemptive thoracic radiotherapy could be a competitive first-line therapeutic option due to superior PFS and favorable safety.

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“…Furthermore, only patients with EGFR mutation or EGFR T790M mutation bene t from the therapeutics, yet only about 36-48% of advanced NSCLC patients in China are EGFR mutation-positive. As a consequence, not all patients can undergo targeted therapy (5). Additionally, the drug resistance of targeted therapies is currently high, which forces us to urgently nd more new targets, so that more lung cancer patients will bene t from targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

A novel defined necroptosis-related lncRNAs signature for predicting the prognosis of non-small cell lung cancer

Zhai

Han

Chen

et al. 2022

Preprint

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Background: Faced with the current poor prognosis of non-small cell lung cancer, this topic attempts to find new potential prognostic biomarkers to improve the situation.Materials and Methods: To form the synthetic matrix, we searched GTEX and The Cancer Genome Atlas for NSCLC transcriptomic data.The necroptosis-related prognostic factor LncRNAs were identified by co-expression analysis and univariate COX regression analysis, and the necroptosis-related LncRNA model was constructed using the least absolute contraction and selection operator (LASSO).Models were then validated using Kaplan-Meier analysis, time-dependent receiver operating characteristics (ROC), univariate COX (uni-COX) regression, multivariate COX (MULTI-COX) regression, nomograms and calibration curves and evaluation.Gene set enrichment analysis (GSEA) was performed in high-risk groups.Results: We constructed a model containing 4 lncRNAs associated with necroptosis.In the model, we found that the calibration map was in good agreement with prognosis prediction.The 1-, 2-, and 3-year survival rates were 0.663, 0.623, and 0.595, respectively.In conclusion, the results of this project support that necroptosis-related lncRNAs can predict prognosis and help to improve individualized treatment of non-small cell lung cancer.Conclusion: Necroptosis-related lncRNAs could help to suggest developable therapeutic strategies that would greatly enhance the level of individualized therapy and improv patient outcomes.

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EGFR‐mutated stage IV non‐small cell lung cancer: What is the role of radiotherapy combined with TKI?

Cited by 10 publications

References 110 publications

MNK/eIF4E inhibition overcomes anlotinib resistance in non‐small cell lung cancer

MNK/eIF4E inhibition overcomes anlotinib resistance in non‐small cell lung cancer

Survival benefit of thoracic radiotherapy plus EGFR-TKIs in patients with non-oligometastatic advanced non-small-cell lung cancer: a single-center retrospective study

A novel defined necroptosis-related lncRNAs signature for predicting the prognosis of non-small cell lung cancer

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