ArticleBritish journal of cancer2005
Synergistic growth inhibition by Iressa and Rapamycin is modulated by VHL mutations in renal cell carcinoma.
Article in British journal of cancer, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00353301 (A Phase II Single Arm Clinical Trial to Evaluate the Efficacy and Safety of the Combination of Tarceva™), which is not on this map. Cited by 20 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.
A Phase II Single Arm Clinical Trial to Evaluate the Efficacy and Safety of the Combination of Tarceva™ (Erlotinib Hydrochloride) and Rapamune™ (Sirolimus) in the Treatment of Metastatic Renal Cell Carcinoma.
Who cites it
20 citing papers in PubMed, 55 citations in OpenAlex.
- Synergistic roles of p53 and HIF1α in human renal cell carcinoma-cell apoptosis responding to the inhibition of mTOR and MDM2 signaling pathways.Drug design, development and therapy · 2016Article
- Evidence for aldosterone-dependent growth of renal cell carcinoma.International journal of experimental pathology · 2014Article
- RASSF6 promotes p21(Cip1/Waf1)-dependent cell cycle arrest and apoptosis through activation of the JNK/SAPK pathway in clear cell renal cell carcinoma.Cell cycle (Georgetown, Tex.) · 2014Article
- AKT kinase pathway: a leading target in cancer research.TheScientificWorldJournal · 2013Review
- The combination of gefitinib and RAD001 inhibits growth of HER2 overexpressing breast cancer cells and tumors irrespective of trastuzumab sensitivity.BMC cancer · 2011Article
- Germline and somatic DNA methylation and epigenetic regulation of KILLIN in renal cell carcinoma.Genes, chromosomes & cancer · 2011Article
- Survival benefit with proapoptotic molecular and pathologic responses from dual targeting of mammalian target of rapamycin and epidermal growth factor receptor in a preclinical model of pancreatic neuroendocrine carcinogenesis.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2010Article
- Safety and efficacy of the combination of erlotinib and sirolimus for the treatment of metastatic renal cell carcinoma after failure of sunitinib or sorafenib.British journal of cancer · 2010Article
- Analysis of VHL Gene Alterations and their Relationship to Clinical Parameters in Sporadic Conventional Renal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2009Article
- Induction of E-cadherin in lung cancer and interaction with growth suppression by histone deacetylase inhibition.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2009Article
- Cytoplasmic sequestration of p27 via AKT phosphorylation in renal cell carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2009Article
- A new role for tamoxifen in oestrogen receptor-negative breast cancer when it is combined with epigallocatechin gallate.British journal of cancer · 2008Article
- Von Hippel-Lindau tumor suppressor gene loss in renal cell carcinoma promotes oncogenic epidermal growth factor receptor signaling via Akt-1 and MEK-1.European urology · 2008Article
- Gene microarray analysis of human renal cell carcinoma: the effects of HDAC inhibition and retinoid treatment.Cancer biology & therapy · 2008Article
- Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human tumours sensitive and resistant to anti-EGFR drugs.British journal of cancer · 2008Article
- Translational up-regulation of the EGFR by tumor hypoxia provides a nonmutational explanation for its overexpression in human cancer.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Overcoming resistance to molecularly targeted anticancer therapies: Rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2007Review
- mTOR and cancer therapy.Oncogene · 2006Review
- Endocytic function of von Hippel-Lindau tumor suppressor protein regulates surface localization of fibroblast growth factor receptor 1 and cell motility.The Journal of biological chemistry · 2006Article
- Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapyReview
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) and tumour growth factor alpha (TGFalpha) are frequently overexpressed in renal cell carcinoma (RCC) yet responses to single-agent EGFR inhibitors are uncommon. Although von Hippel-Lindau (VHL) mutations are predominant, RCC also develops in individuals with tuberous sclerosis (TSC). Tuberous sclerosis mutations activate mammalian target of rapamycin (mTOR) and biochemically resemble VHL alterations. We found that RCC cell lines expressed EGFR mRNA in the near-absence of other ErbB family members. Combined EGFR and mTOR inhibition synergistically impaired growth in a VHL-dependent manner. Iressa blocked ERK1/2 phosphorylation specifically in wt-VHL cells, whereas rapamycin inhibited phospho-RPS6 and 4E-BP1 irrespective of VHL. In contrast, phospho-AKT was resistant to these agents and MYC translation initiation (polysome binding) was similarly unaffected unless AKT was inhibited. Primary RCCs vs cell lines contained similar amounts of phospho-ERK1/2, much higher levels of ErbB-3, less phospho-AKT, and no evidence of phospho-RPS6, suggesting that mTOR activity was reduced. A subset of tumours and cell lines expressed elevated eIF4E in the absence of upstream activation. Despite similar amounts of EGFR mRNA, cell lines (vs tumours) overexpressed EGFR protein. In the paired cell lines, PRC3 and WT8, EGFR protein was elevated post-transcriptionally in the VHL mutant and EGF-stimulated phosphorylation was prolonged. We propose that combined EGFR and mTOR inhibitors may be useful in the subset of RCCs with wt-VHL. However, apparent differences between primary tumours and cell lines require further investigation.
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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.