ArticleBMC cancer2014
Phosphorylation of mTOR and S6RP predicts the efficacy of everolimus in patients with metastatic renal cell carcinoma.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01152801 (A Phase Ib, Multi-center, Open-label Study to Evaluate the Safety of RAD001 in Chinese Patients With Metastatic Renal Cell Cancer Who Are Intolerant of or Who Have Progressed Despite Treatment With VEGF-targeted Therapies), which is not on this map. Cited by 28 papers, 1 of them a synthesis 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.
A Phase Ib, Multi-center, Open-label Study to Evaluate the Safety of RAD001 in Chinese Patients With Metastatic Renal Cell Cancer Who Are Intolerant of or Who Have Progressed Despite Treatment With VEGF-targeted Therapies
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Pooled it
- Phase II study of everolimus (RAD001) monotherapy as first-line treatment in advanced biliary tract cancer with biomarker exploration: the RADiChol Study.British journal of cancer · 2018Trial
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- Retrospective immunophenotypical evaluation of MET, PD-1/PD-L1, and mTOR pathways in primary tumors and pulmonary metastases of renal cell carcinoma: the RIVELATOR study addresses the issue of biomarkers heterogeneity.Exploration of targeted anti-tumor therapy · 2023Article
- The Role of Autophagy in Osteoarthritic Cartilage.Biomolecules · 2022Review
- Case Report: Extensive Tumor Profiling in Primary Neuroendocrine Breast Cancer Cases as a Role Model for Personalized Treatment in Rare and Aggressive Cancer Types.Frontiers in medicine · 2022Article
- Features of increased malignancy in eosinophilic clear cell renal cell carcinoma.The Journal of pathology · 2020Article
- Targeted Therapy Recommendations for Therapy Refractory Solid Tumors-Data from the Real-World Precision Medicine Platform MONDTI.Journal of personalized medicine · 2020Article
- Metastatic role of mammalian target of rapamycin signaling activation by chemoradiotherapy in advanced rectal cancer.Cancer science · 2020Article
- Fluvastatin potentiates anticancer activity of vorinostat in renal cancer cells.Cancer science · 2020Article
- mTOR and mTOR phosphorylation status in primary and metastatic renal cell carcinoma tissue: differential expression and clinical relevance.Journal of cancer research and clinical oncology · 2019Article
- Hierarchical clustering of activated proteins in the PI3K and MAPK pathways in ER-positive, HER2-negative breast cancer with potential therapeutic consequences.British journal of cancer · 2018Article
- Prognostic and predictive role of the PI3K-AKT-mTOR pathway in neuroendocrine neoplasms.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Review
- EGFR and AKT1 overexpression are mutually exclusive and associated with a poor survival in resected gastric adenocarcinomas.Cancer biomarkers : section A of Disease markers · 2018Article
- Therapeutic Effect of Repurposed Temsirolimus in Lung Adenocarcinoma Model.Frontiers in pharmacology · 2018Article
- Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action.Targeted oncology · 2017Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe incidence of renal cell cancer (RCC) has been increasing for the past decade, and the 5-year survival for patients with metastatic RCC (mRCC) is rather low. Everolimus (RAD001), a new inhibitor for mammalian target of rapamycin (mTOR), is generally well tolerated, and demonstrates clinical benefit to patients with anti-VEGF-refractory mRCC. However, factors for selection of patients who may benefit from everolimus remain largely unknown. Here we aimed to explore potential molecular indicators for mRCC patients who may benefit from everolimus treatment.
methodsParaffin-embedded tumor tissue specimens derived from 18 mRCC patients before everolimus treatment, who participated the phase 1b trial of everolimus in VEGF receptor (VEGFR)-tyrosine kinase inhibitor (TKI)-refractory Chinese patients with mRCC (clinicaltrials.gov, NCT01152801), were examined for the expression levels of phosphorylated AKT, mTOR, eukaryotic initiation factor 4E (eIF4E) binding protein-1 (4EBP1) and 40S ribosomal protein S6 (S6RP) by immunohistochemistry. Clinical benefit rate (complete response [CR], partial response [PR], plus stable disease [SD] ≥ 6 months) and progression-free survival time (PFS) were correlated with expression levels of these mTOR-associated molecules.
resultsIn these 18 patients, there were 1 PR, 15 SDs (including 9 SDs ≥ 6 months), and 2 progressive diseases (PD). The clinical benefit rate (CBR) was 55.6% (10/18), and the median PFS time was 8.4 months. Patients with positive expression of phospho-mTOR showed a better CBR (71.4% versus 0%, P = 0.023) and PFS time (11.3 versus 3.7 months, P = 0.001) than those patients with negative expression. The median PFS of patients with positive phospho-S6RP expression was longer (11.3 versus 3.7 months, P = 0.002) than that of patients negative for phospho-S6RP expression. However, expression levels of phospho-4EBP1 and phospho-AKT were unassociated to efficacy of everolimus treatment with respect to CBR and PFS. Co-expression of phosphorylated mTOR, S6RP and/or 4EBP1 may improve the predictive value of the biomarkers for patients treated with everolimus.
conclusionsThe expression levels of phospho-mTOR and phospho-S6RP may be potential predictive biomarkers for efficacy of everolimus in patients with mRCC. Combining examinations of phosphorylated mTOR, S6RP and/or 4EBP1 may be a potential strategy to select mRCC patients sensitive to mTOR inhibitor treatment.
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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.