ArticleCell cycle (Georgetown, Tex.)2016
STAT3-targeted treatment with silibinin overcomes the acquired resistance to crizotinib in ALK-rearranged lung cancer.
Article in Cell cycle (Georgetown, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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
39 citing papers in PubMed, 62 citations in OpenAlex.
- Luteolin enhances antitumor immunity of B7-H3-targeted bispecific natural killer cell engagers against non-small cell lung cancer.International journal of biological sciences · 2026Article
- Unveiling the therapeutic potential of silibinin in head and neck squamous cell carcinoma via network pharmacology.Scientific reports · 2025Article
- Fangchinoline-mediated autophagy inhibition amplifies antigen presentation and PD-1 blockade efficacy in lung cancer.Acta pharmacologica Sinica · 2025Article
- Silibinin enhanced the efficacy of albendazole in treating the muscular phase of experimental trichinellosis.Tropical animal health and production · 2025Article
- Flavonoids in the Treatment of Non-small Cell Lung Cancer via Immunomodulation: Progress to Date.Molecular diagnosis & therapy · 2025Review
- The Effects of Silibinin Combined With EGFR-TKIs in the Treatment of NSCLC.Cancer medicine · 2025Review
- Natural products as metabolic modulators to enhance cancer immunotherapy: reprogramming the tumor microenvironment.Frontiers in immunology · 2025Review
- Bioactive components and delivery strategies of food-medicine homologous substances in lung cancer therapy: current advances and clinical translation.Frontiers in nutrition · 2025Review
- The Role of Nutraceuticals in Chemoprevention and their Therapeutic Effects when used in Combination with Synthetic Drugs.Current medicinal chemistry · 2025Review
- Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review.Cell death & disease · 2024Review
- From immune checkpoints to therapies: understanding immune checkpoint regulation and the influence of natural products and traditional medicine on immune checkpoint and immunotherapy in lung cancer.Frontiers in immunology · 2024Review
- ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- A review of natural products targeting tumor immune microenvironments for the treatment of lung cancer.Frontiers in immunology · 2024Review
- Anti-Cancer Potential of Phytochemicals: The Regulation of the Epithelial-Mesenchymal Transition.Molecules (Basel, Switzerland) · 2023Review
- Overcoming Acquired Drug Resistance to Cancer Therapies through Targeted STAT3 Inhibition.International journal of molecular sciences · 2023Review
- Silibinin Overcomes EMT-Driven Lung Cancer Resistance to New-Generation ALK Inhibitors.Cancers · 2022Article
- Silibinin Suppresses the Hyperlipidemic Effects of the ALK-Tyrosine Kinase Inhibitor Lorlatinib in Hepatic Cells.International journal of molecular sciences · 2022Article
- Emerging role of natural products in cancer immunotherapy.Acta pharmaceutica Sinica. B · 2022Review
- An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance.Bosnian journal of basic medical sciences · 2022Review
- Sesquiterpene Lactones Attenuate Paclitaxel Resistance Via Inhibiting MALAT1/STAT3/ FUT4 Axis and P-Glycoprotein Transporters in Lung Cancer Cells.Frontiers in pharmacology · 2022Article
Corrections and comments
- Commented on by
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The signal transducer and activator of transcription 3 (STAT3) has been suggested to play a prominent role in mediating non-small-cell lung cancer (NSCLC) resistance to some tyrosine kinase inhibitor (TKI)-mediated therapies. Using a model of anaplastic lymphoma kinase gene (ALK)-translocated NSCLC with acquired resistance to the ALK TKI crizotinib, but lacking amplifications or mutations in the kinase domain of ALK, we herein present evidence that STAT3 activation is a novel mechanism of crizotinib resistance that involves the upregulation of immune escape and epithelial to mesenchymal transition (EMT) signaling pathways. Taking advantage of the flavonolignan silibinin as a naturally occurring STAT3-targeted pharmacological inhibitor, we confirmed that STAT3 activation protects ALK-translocated NSCLC from crizotinib. Accordingly, silibinin-induced inhibition of STAT3 worked synergistically with crizotinib to reverse acquired resistance and restore sensitivity in crizotinib-resistant cells. Moreover, silibinin treatment significantly inhibited the upregulation of the immune checkpoint regulator PD-L1 and also EMT regulators (e.g., SLUG, VIM, CD44) in crizotinib-refractory cells. These findings provide a valuable strategy to potentially improve the efficacy of ALK inhibition by cotreatment with silibinin-based therapeutics, which merit clinical investigation for ALK TKI-resistant NSCLC patients.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.