ArticleCancer research2011
Sorafenib enhances pemetrexed cytotoxicity through an autophagy-dependent mechanism in cancer cells.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 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
56 citing papers in PubMed, 108 citations in OpenAlex.
- Pharmacogenomic insights: IL-23R and ATG-10 polymorphisms in Sorafenib response for hepatocellular carcinoma.Clinical and experimental medicine · 2025Trial
- Cellular and molecular mechanisms of arenobufagin in cancer therapy: a systematic review.Discover oncology · 2025Review
- Autophagy-based therapy for hepatocellular carcinoma: from standard treatments to combination therapy, oncolytic virotherapy, and targeted nanomedicines.Clinical and experimental medicine · 2024Review
- Cannabidiol regulates apoptosis and autophagy in inflammation and cancer: A review.Frontiers in pharmacology · 2023Review
- Small Molecule Inhibitors for Hepatocellular Carcinoma: Advances and Challenges.Molecules (Basel, Switzerland) · 2022Review
- Iron commensalism of mesenchymal glioblastoma promotes ferroptosis susceptibility upon dopamine treatment.Communications biology · 2022Article
- Osimertinib-resistant NSCLC cells activate ERBB2 and YAP/TAZ and are killed by neratinib.Biochemical pharmacology · 2021Article
- Autophagy in liver diseases.World journal of hepatology · 2021Review
- GZ17-6.02 and Pemetrexed Interact to Kill Osimertinib-Resistant NSCLC Cells That Express Mutant ERBB1 Proteins.Frontiers in oncology · 2021Article
- The role of cell signaling in the crosstalk between autophagy and apoptosis in the regulation of tumor cell survival in response to sorafenib and neratinib.Seminars in cancer biology · 2020Review
- Discovery of N-phenyl-(2,4-dihydroxypyrimidine-5-sulfonamido) phenylurea-based thymidylate synthase (TS) inhibitor as a novel multi-effects antitumor drugs with minimal toxicity.Cell death & disease · 2019Article
- Diverse Functions of Autophagy in Liver Physiology and Liver Diseases.International journal of molecular sciences · 2019Review
- Kinase inhibitors: look beyond the label on the bottle.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Palbociclib augments Neratinib killing of tumor cells that is further enhanced by HDAC inhibition.Cancer biology & therapy · 2019Article
- Gene and MicroRNA Perturbations of Cellular Response to Pemetrexed Implicate Biological Networks and Enable Imputation of Response in Lung Adenocarcinoma.Scientific reports · 2018Article
- Autophagy Modulation in Cancer: Current Knowledge on Action and Therapy.Oxidative medicine and cellular longevity · 2018Review
- Autophagy orchestrates adaptive responses to targeted therapy in endometrial cancer.Autophagy · 2017Article
- PDE5 inhibitors enhance the lethality of [pemetrexed + sorafenib].Oncotarget · 2017Article
- PDE5 inhibitors enhance the lethality of pemetrexed through inhibition of multiple chaperone proteins and via the actions of cyclic GMP and nitric oxide.Oncotarget · 2017Article
- Phase I study of pemetrexed with sorafenib in advanced solid tumors.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Pemetrexed (ALIMTA, Lilly) is a folate antimetabolite that has been approved by the U.S. Food and Drug Administration for the treatment of non-small cell lung cancer and has been shown to stimulate autophagy. In the present study, we sought to further understand the role of autophagy in response to pemetrexed and to test if combination therapy could enhance the level of toxicity through altered autophagy in tumor cells. The multikinase inhibitor sorafenib (Nexavar, Bayer), used in the treatment of renal and hepatocellular carcinoma, suppresses tumor angiogenesis and promotes autophagy in tumor cells. We found that sorafenib interacted in a greater than additive fashion with pemetrexed to increase autophagy and to kill a diverse array of tumor cell types. Tumor cell types that displayed high levels of cell killing after combination treatment showed elevated levels of AKT, p70 S6K, and/or phosphorylated mTOR, in addition to class III receptor tyrosine kinases such as platelet-derived growth factor receptor beta and VEGF receptors, known in vivo targets of sorafenib. In xenograft and in syngeneic animal models of mammary carcinoma and glioblastoma, the combination of sorafenib and pemetrexed suppressed tumor growth without deleterious effects on normal tissues or animal body mass. Taken together, the data suggest that premexetred and sorafenib act synergistically to enhance tumor killing via the promotion of a toxic form of autophagy that leads to activation of the intrinsic apoptosis pathway, and predict that combination treatment represents a future therapeutic option in the treatment of solid tumors.
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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.