ArticleInternational journal of cancer2014
Preclinical trial of a new dual mTOR inhibitor, MLN0128, using renal cell carcinoma tumorgrafts.
Article in International journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 3 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 3 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- Pooled it
- mTOR Inhibitors in Castration-Resistant Prostate Cancer: A Systematic Review.Targeted oncology · 2017Pooled it
- Cancer stem cell markers predict a poor prognosis in renal cell carcinoma: a meta-analysis.Oncotarget · 2016Pooled it
- Drug repurposing as a promising therapeutic strategy against renal cell carcinoma.Cancer chemotherapy and pharmacology · 2026Review
- The mechanism of the PI3K-AKT-mTOR signaling pathway in renal cell carcinoma: current developments and future prospects.Frontiers in oncology · 2026Review
- The Precision-Guided Use of PI3K Pathway Inhibitors for the Treatment of Solid Malignancies.Biomedicines · 2025Review
- Identification of Molecular Subtypes of Clear-Cell Renal Cell Carcinoma in Patient-Derived Xenografts Using Multi-Omics.Cancers · 2025Article
- Targeting mTOR as a Cancer Therapy: Recent Advances in Natural Bioactive Compounds and Immunotherapy.Cancers · 2022Review
- Identification of New Vulnerabilities in Conjunctival Melanoma Using Image-Based High Content Drug Screening.Cancers · 2022Article
- A Phase 1 Study of Sapanisertib (TAK-228) in East Asian Patients with Advanced Nonhematological Malignancies.Targeted oncology · 2022Article
- Inhibition of the HIF-1 Survival Pathway as a Strategy to Augment Photodynamic Therapy Efficacy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- A renal cell carcinoma tumorgraft platform to advance precision medicine.Cell reports · 2021Article
- Article
- Mechanistic Target of Rapamycin Inhibitors in Renal Cell Carcinoma: Potential, Limitations, and Perspectives.Frontiers in cell and developmental biology · 2021Review
- Preclinical and Dose-Finding Phase I Trial Results of Combined Treatment with a TORC1/2 Inhibitor (TAK-228) and Aurora A Kinase Inhibitor (Alisertib) in Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Oxygen: viral friend or foe?Virology journal · 2020Review
- Patient-Derived Xenograft Models in Urological Malignancies: Urothelial Cell Carcinoma and Renal Cell Carcinoma.Cancers · 2020Review
- Patient-derived xenograft models to optimize kidney cancer therapies.Translational andrology and urology · 2019Review
- The 'Achilles Heel' of Metabolism in Renal Cell Carcinoma: Glutaminase Inhibition as a Rational Treatment Strategy.Kidney cancer (Clifton, Va.) · 2019Review
- Co-expression of Cancer Stem Cell Markers OCT4 and NANOG Predicts Poor Prognosis in Renal Cell Carcinomas.Scientific reports · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 4 countries.
Funding
Abstract
mTOR is a rational target in renal cell carcinoma (RCC) because of its role in disease progression. However, the effects of temsirolimus, the only first-generation mTOR inhibitor approved by the FDA for first-line treatment of metastatic RCC, on tumor reduction and progression-free survival are minimal. Second-generation mTOR inhibitors have not been evaluated on RCC. We compared the effects of temsirolimus and MLN0128, a potent second-generation mTOR inhibitor, on RCC growth and metastasis using a realistic patient-derived tissue slice graft (TSG) model. TSGs were derived from three fresh primary RCC specimens by subrenal implantation of precision-cut tissue slices into immunodeficient mice that were randomized and treated with MLN0128, temsirolimus, or placebo. MLN0128 consistently suppressed primary RCC growth, monitored by magnetic resonance imaging (MRI), in three TSG cohorts for up to 2 months. Temsirolimus, in contrast, only transiently inhibited the growth of TSGs in one of two cohorts before resistance developed. In addition, MLN0128 reduced liver metastases, determined by human-specific quantitative polymerase chain reaction, in two TSG cohorts, whereas temsirolimus failed to have any significant impact. Moreover, MLN0128 decreased levels of key components of the two mTOR subpathways including TORC1 targets 4EBP1, p-S6K1, HIF1α and MTA1 and the TORC2 target c-Myc, consistent with dual inhibition. Our results demonstrated that MLN0128 is superior to temsirolimus in inhibiting primary RCC growth as well as metastases, lending strong support for further clinical development of dual mTOR inhibitors for RCC treatment.
Indexed as
Identifiers
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.