ArticleCancer biology & therapy2019
Fingolimod augments Pemetrexed killing of non-small cell lung cancer and overcomes resistance to ERBB inhibition.
Article in Cancer biology & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Serum sphingosine-1-phosphate levels are associated with brain metastasis inFuture oncology (London, England) · 2025Article
- Sphingolipid metabolism dysregulation: A cause for lung cancer development, progression, and resistance to therapies.Chinese medical journal pulmonary and critical care medicine · 2025Review
- Lentinan mitigates pemetrexed chemoresistance by the PI3K/Akt pathway in non-small cell lung cancer.Cell biochemistry and biophysics · 2024Article
- Effect of FTY-720 on Pulmonary Fibrosis in Mice via the TGF-β1 Signaling Pathway and Autophagy.Biomolecules & therapeutics · 2023Article
- Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Non-Small Cell Lung Cancer Preclinical Models.International journal of molecular sciences · 2022Article
- Molecular Pharmacology and Novel Potential Therapeutic Applications of Fingolimod.Frontiers in pharmacology · 2022Review
- Sphingolipid Metabolism and Signaling in Lung Cancer: A Potential Therapeutic Target.Journal of oncology · 2022Review
- Implications of Sphingolipids on Aging and Age-Related Diseases.Frontiers in aging · 2021Review
- The CAGE-MiR-181b-5p-S1PR1 Axis Regulates Anticancer Drug Resistance and Autophagy in Gastric Cancer Cells.Frontiers in cell and developmental biology · 2021Article
- Targeting Sphingolipids for Cancer Therapy.Frontiers in oncology · 2021Review
- Article
- Druggable Sphingolipid Pathways: Experimental Models and Clinical Opportunities.Advances in experimental medicine and biology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Overall, NSCLC has a poor 5-year survival and new therapeutic approaches are urgently needed. ERBB-addicted NSCLC that have become resistant to ERBB inhibitors are often refractory to additional therapeutic interventions. The sphingosine-1-phosphate receptor modulator fingolimod (FTY720), approved for the treatment of multiple sclerosis, synergized with the NSCLC therapeutic pemetrexed to kill NSCLC and ovarian cancer cells. This occurred in lung cancer cells expressing mutated K-RAS, mutated ERBB1, or in NSCLC cells resistant to afatinib (an ERBB1/2/4 inhibitor). This drug combination appeared to use overlapping and distinct mechanisms of killing in different cell lines. Activation of AMP-dependent kinase (AMPK) and reduced expression and inactivation of mTOR were associated with increased autophagosome and autolysosome formation. Downregulation of Beclin1 considerably reduced formation of autophagosomes and protected the cells from drug combination-induced killing without significantly altering autolysosome formation. Autophagy protein 5 (ATG5) knock down afforded greater protection against the combination of pemetrexed with fingolimod. Treatment of cells with the mTOR inhibitor everolimus markedly enhanced the lethality of pemetrexed plus fingolimod combination. Our data suggest that the combination of fingolimod with the established NSCLC/ovarian cancer drug pemetrexed should be explored as a new therapy.
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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.