ArticleOncotarget2016
[Pemetrexed + Sorafenib] lethality is increased by inhibition of ERBB1/2/3-PI3K-NFκB compensatory survival signaling.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01450384 (Phase I Study of Pemetrexed and Sorafenib in Advanced Malignancy), which is not on this map. Cited by 23 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.
Phase I Study of Pemetrexed and Sorafenib in Advanced Malignancy
Who cites it
23 citing papers in PubMed, 28 citations in OpenAlex.
- Screening of signaling pathways and hub genes in Guillain-Barré syndrome based on bioinformatics and machine learning.BMC neurology · 2026Article
- Article
- Antiaging gene Klotho regulates epithelial-mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin-2 expression.Oncology letters · 2021Article
- Axitinib and HDAC Inhibitors Interact to Kill Sarcoma Cells.Frontiers in oncology · 2021Article
- 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
- GZ17-6.02 and Doxorubicin Interact to Kill Sarcoma Cells via Autophagy and Death Receptor Signaling.Frontiers in oncology · 2020Article
- Not the comfy chair! Cancer drugs that act against multiple active sites.Expert opinion on therapeutic targets · 2019Review
- Fingolimod augments Pemetrexed killing of non-small cell lung cancer and overcomes resistance to ERBB inhibition.Cancer biology & therapy · 2019Article
- Kinase inhibitors: look beyond the label on the bottle.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- NEDD4 over-expression regulates the afatinib resistant phenotype of NSCLC cells.Oncology signaling · 2018Article
- Unconventional Approaches to Modulating the Immunogenicity of Tumor Cells.Advances in cancer research · 2018Review
- Curcumin interacts with sildenafil to kill GI tumor cells via endoplasmic reticulum stress and reactive oxygen/ nitrogen species.Oncotarget · 2017Article
- HDAC inhibitors enhance neratinib activity and when combined enhance the actions of an anti-PD-1 immunomodulatory antibodyOncotarget · 2017Article
- The anti-neoplastic activity of Vandetanib against high-risk medulloblastoma variants is profoundly enhanced by additional PI3K inhibition.Oncotarget · 2017Article
- The HDAC inhibitor AR42 interacts with pazopanib to kill trametinib/dabrafenib-resistant melanoma cells in vitro and in vivo.Oncotarget · 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
- AR-12 Inhibits Multiple Chaperones Concomitant With Stimulating Autophagosome Formation Collectively Preventing Virus Replication.Journal of cellular physiology · 2016Article
- Phase I study of pemetrexed with sorafenib in advanced solid tumors.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
In the completed phase I trial NCT01450384 combining the anti-folate pemetrexed and the multi-kinase inhibitor sorafenib it was observed that 20 of 33 patients had prolonged stable disease or tumor regression, with one complete response and multiple partial responses. The pre-clinical studies in this manuscript were designed to determine whether [pemetrexed + sorafenib] -induced cell killing could be rationally enhanced by additional signaling modulators. Multiplex assays performed on tumor material that survived and re-grew after [pemetrexed + sorafenib] exposure showed increased phosphorylation of ERBB1 and of NFκB and IκB; with reduced IκB and elevated G-CSF and KC protein levels. Inhibition of JAK1/2 downstream of the G-CSF/KC receptors did not enhance [pemetrexed + sorafenib] lethality whereas inhibition of ERBB1/2/4 using kinase inhibitory agents or siRNA knock down of ERBB1/2/3 strongly promoted killing. Inhibition of ERBB1/2/4 blocked [pemetrexed + sorafenib] stimulated NFκB activation and SOD2 expression; and expression of IκB S32A S36A significantly enhanced [pemetrexed + sorafenib] lethality. Sorafenib inhibited HSP90 and HSP70 chaperone ATPase activities and reduced the interactions of chaperones with clients including c-MYC, CDC37 and MCL-1. In vivo, a 5 day transient exposure of established mammary tumors to lapatinib or vandetanib significantly enhanced the anti-tumor effect of [pemetrexed + sorafenib], without any apparent normal tissue toxicities. Identical data to that in breast cancer were obtained in NSCLC tumors using the ERBB1/2/4 inhibitor afatinib. Our data argue that the combination of pemetrexed, sorafenib and an ERBB1/2/4 inhibitor should be explored in a new phase I trial in solid tumor patients.
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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.