ArticleCancer science2010
Significance of thymidylate synthase for resistance to pemetrexed in lung cancer.
Article in Cancer science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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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
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Pooled it
- Phase II Study of Pemetrexed as a Salvage Chemotherapy for Thymidylate Synthase-Low Squamous Cell Lung Cancer.Cancer research and treatment · 2021Trial
- Does histology predict survival of advanced non-small cell lung cancer patients treated with platin-based chemotherapy? An analysis of the Eastern Cooperative Oncology Group Study E1594.Lung cancer (Amsterdam, Netherlands) · 2013Trial
- Diffuse and Strong TTF-1 Expression Predicts Response to Pemetrexed-Based Immunochemotherapy in Advanced Lung Adenocarcinoma.Cancer management and research · 2025Article
- Article
- Anticancer Activity of Imidazolyl Gold(I/III) Compounds in Non-Small Cell Lung Cancer Cell Lines.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Activity of pemetrexed in pre-clinical chordoma models and humans.Scientific reports · 2023Article
- Picropodophyllin inhibits the growth of pemetrexed-resistant malignant pleural mesothelioma via microtubule inhibition and IGF-1R-, caspase-independent pathways.Translational lung cancer research · 2022Article
- Uncovering cancer vulnerabilities by machine learning prediction of synthetic lethality.Molecular cancer · 2021Article
- Design and Analysis of Cancer Clinical Trials for Personalized Medicine.Journal of personalized medicine · 2021Review
- A long-term survivor keeping in a complete response without treatment after pemetrexed maintenance therapy for advanced non-squamous non-small cell lung cancer.Clinical case reports · 2021Article
- Thymidylate synthase drives the phenotypes of epithelial-to-mesenchymal transition in non-small cell lung cancer.British journal of cancer · 2021Article
- Antimetabolite pemetrexed primes a favorable tumor microenvironment for immune checkpoint blockade therapy.Journal for immunotherapy of cancer · 2020Article
- Mechanisms of resistance to pemetrexed in non-small cell lung cancer.Translational lung cancer research · 2019Review
- Building a Bridge between Chemotherapy and Immunotherapy in Malignant Pleural Mesothelioma: Investigating the Effect of Chemotherapy on Immune Checkpoint Expression.International journal of molecular sciences · 2019Article
- Prediction of response to pemetrexed in non-small-cell lung cancer with immunohistochemical phenotyping based on gene expression profiles.BMC cancer · 2019Article
- FGF2-FGFR1 pathway activation together with thymidylate synthase upregulation is induced in pemetrexed-resistant lung cancer cells.Oncotarget · 2019Article
- Dihydrofolate reductase as a predictor for poor response to platinum-based chemotherapy in epithelial ovarian cancer.International journal of clinical and experimental pathology · 2019Article
- Integrated Bioinformatics Analysis of Hub Genes and Pathways in Anaplastic Thyroid Carcinomas.International journal of endocrinology · 2019Article
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pemetrexed (MTA) is a multitargeted antifolate with promising clinical activity in lung cancer. We exposed the small cell lung cancer cell line PC6 to stepwise-increasing pemetrexed concentrations of 0.4, 1.6, and 4.0 microm, and established three pemetrexed-resistant lung cancer cell lines: PC6/MTA-0.4, PC6/MTA-1.6, and PC6/MTA-4.0 cells. To investigate the mechanisms of acquired resistance to pemetrexed, we measured the expression levels of the thymidylate synthase (TS), reduced folate carrier (RFC), and folylpoly-gamma-glutamate synthetase (FPGS) genes. TS gene expression was significantly increased in PC6/MTA-1.6 and PC6/MTA-4.0 cells relative to parental cells in a pemetrexed dose-dependent manner. In contrast, the levels of RFC gene expression in PC6/MTA-0.4 cells and FPGS in PC6/MTA-1.6 cells were significantly decreased, whereas the levels of both genes were restored in PC6/MTA-4.0 cells. Knockdown of TS expression using siRNA enhanced pemetrexed cytotoxicity in PC6/MTA-4.0 cells. The expression level of the TS gene was significantly correlated with the concentration of pemetrexed for 50% cell survival (IC(50)) in 11 non-small cell lung cancer cell lines. These results suggest that the alteration of molecular pharmacological factors in relation with pemetrexed resistance is dose-dependent, and that up-regulation of the expression of the TS gene may have an important role in the acquired resistance to pemetrexed. In addition, TS may be a predictive marker for pemetrexed sensitivity in lung cancer.
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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.