ArticleOncotarget2014
Rapamycin downregulates thymidylate synthase and potentiates the activity of pemetrexed in non-small cell lung cancer.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Rational application of the first-line chemotherapy and immune checkpoint inhibitors in advanced nonsmall cell lung cancer: A meta-analysis.Cancer medicine · 2019Pooled it
- Anti-PD-1/PD-L1 antibody therapy for pretreated advanced nonsmall-cell lung cancer: A meta-analysis of randomized clinical trials.Medicine · 2016Pooled it
- Rhodosporidium toruloides-a new surrogate model to study rapamycin induced effects on human aging and cancer.Cellular and molecular life sciences : CMLS · 2025Article
- Genetic variants in LKB1/AMPK/mTOR pathway are associated with clinical outcomes of chemotherapy in non-small cell lung cancer.Thoracic cancer · 2022Article
- Low Temperature Plasma Suppresses Lung Cancer Cells Growth via VEGF/VEGFR2/RAS/ERK Axis.Molecules (Basel, Switzerland) · 2022Article
- Construction of an immune-related lncRNA signature pair for predicting oncologic outcomes and the sensitivity of immunosuppressor in treatment of lung adenocarcinoma.Respiratory research · 2022Article
- TOR Inhibitors Synergistically Suppress the Growth and Development ofFrontiers in microbiology · 2021Article
- A phase I/II study of pemetrexed with sirolimus in advanced, previously treated non-small cell lung cancer.Translational lung cancer research · 2019Article
- Disparate effects of cytotoxic chemotherapy on the antiviral activity of antiretroviral therapy: implications for treatments of HIV-infected cancer patients.Antiviral therapy · 2019Article
- mTOR mediates a mechanism of resistance to chemotherapy and defines a rational combination strategy to treat KRAS-mutant lung cancer.Oncogene · 2019Article
- Coronary Toxicities of Anti-PD-1 and Anti-PD-L1 Immunotherapies: a Case Report and Review of the Literature and International Registries.Targeted oncology · 2018Review
- Connective tissue growth factor-specific monoclonal antibody inhibits growth of malignant mesothelioma in an orthotopic mouse model.Oncotarget · 2018Article
- Sialic acid-binding lectin from bullfrog eggs inhibits human malignant mesothelioma cell growth in vitro and in vivo.PloS one · 2018Article
- Role of Autophagy and Apoptosis in Non-Small-Cell Lung Cancer.International journal of molecular sciences · 2017Review
- Dasatinib modulates sensitivity to pemetrexed in malignant pleural mesothelioma cell lines.Oncotarget · 2016Article
- A Phase I Trial of Temsirolimus and Pemetrexed in Patients with Advanced Non-Small Cell Lung Cancer.Chemotherapy · 2016Article
- CMTM7 knockdown increases tumorigenicity of human non-small cell lung cancer cells and EGFR-AKT signaling by reducing Rab5 activation.Oncotarget · 2015Article
- A strategy for the identification of combinatorial bioactive compounds contributing to the holistic effect of herbal medicines.Scientific reports · 2015Article
- Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone.Oncotarget · 2015Article
- Effect of rapamycin (RAPA) on the growth of lung cancer and its mechanism in mice with A549.International journal of clinical and experimental pathology · 2015Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancer cases, and almost half of newly diagnosed patients have metastatic disease. Pemetrexed is a widely used drug for NSCLC and inhibits several folate-dependent enzymes including thymidylate synthase (TS). Increased expression of TS confers resistance to pemetrexed in vitro and predicts poor response to pemetrexed. Rapamycin is an mTOR inhibitor and suppresses cap-dependent synthesis of specific mRNA species. Here, we show that the combination of rapamycin and pemetrexed synergistically inhibits proliferation of NSCLC cells. Although pemetrexed as a single agent induced TS, pretreatment with rapamycin suppressed pemetrexed-induced TS expression. In vivo, the combination of rapamycin and pemetrexed inhibited growth of NSCLC xenografts, which correlated with decreased mTOR activity and suppression of pemetrexed-induced TS expression. The ability of rapamycin to enhance the efficacy of pemetrexed and prevent TS expression has implications for the design of Phase I and/or Phase II NSCLC clinical trials with mTOR inhibitors in combination with pemetrexed.
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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.