SynthesisTargeted oncology2017
mTOR Inhibitors in Castration-Resistant Prostate Cancer: A Systematic Review.
Synthesis in Targeted oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 65 citations in OpenAlex.
- CDK4-selective inhibitor AU2-94 for the treatment of advanced and therapy-resistant prostate cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Extracellular vesicles from prostate tumors reshape the pre-metastatic bone environment in an mTOR/RAB1A-dependent manner.Frontiers in immunology · 2025Article
- Identification of KLHL17 as a prognostic marker for prostate cancer based on single-cell sequencing and in vitro/in vivo experiments.Discover oncology · 2024Article
- Exploring potential therapeutic combinations for castration-sensitive prostate cancer using supercomputers: a proof of concept study.Scientific reports · 2024Article
- A common molecular and cellular pathway in developing Alzheimer and cancer.Biochemistry and biophysics reports · 2024Review
- The Rapidly Evolving Treatment Landscape of Metastatic Hormone-Sensitive Prostate Cancer.Clinical Medicine Insights. Oncology · 2024Review
- STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway.Molecular cancer · 2023Article
- Pharmacological inhibition of the SKP2/p300 signaling axis restricts castration-resistant prostate cancer.Neoplasia (New York, N.Y.) · 2023Article
- Long-term disease stability with bicalutamide in a man with aggressive angiomyxoma: case report and state of art.Frontiers in oncology · 2023Article
- Development of machine learning classifiers to predict compound activity on prostate cancer cell lines.Journal of cheminformatics · 2022Article
- PTEN Protein Phosphatase Activity Is Not Required for Tumour Suppression in the Mouse Prostate.Biomolecules · 2022Article
- Capsaicin Alters the Expression of Genetic and Epigenetic Molecules In Hepatocellular Carcinoma Cell.International journal of molecular and cellular medicine · 2022Article
- Prostate Cancer Immunotherapy-Finally in From the Cold?Current oncology reports · 2021Review
- Article
- Case Report: Systemic Treatment and Serial Genomic Sequencing of Metastatic Prostate Adenocarcinoma Progressing to Small Cell Carcinoma.Frontiers in oncology · 2021Article
- Dual Inhibition of mTORC1/2 Reduces Migration of Cholangiocarcinoma Cells by Regulation of Matrixmetalloproteinases.Frontiers in cell and developmental biology · 2021Article
- Pharmacological Inhibition of mTORC2 Reduces Migration and Metastasis in Melanoma.International journal of molecular sciences · 2020Article
- Mechanisms of Androgen Receptor Agonist- and Antagonist-Mediated Cellular Senescence in Prostate Cancer.Cancers · 2020Review
- Double-Negative Prostate Cancer Masquerading as a Squamous Cancer of Unknown Primary: A Clinicopathologic and Genomic Sequencing-Based Case Study.JCO precision oncology · 2020Article
- Dual-mTOR Inhibitor Rapalink-1 Reduces Prostate Cancer Patient-Derived Xenograft Growth and Alters Tumor Heterogeneity.Frontiers in oncology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe progression of prostate cancer to castration-resistant prostate cancer (CRPC) is often a result of somatic alterations in the PI3K/Akt/mTOR (mammalian target of rapamycin) pathway, suggesting that therapies targeting this pathway might lead to improved survival and efficacy. Here, we systematically evaluate the results of clinical trials investigating mTOR inhibition in CRPC and utilize preclinical data to predict clinical outcomes.
methodsTrials included in the study were identified through PubMed and via review of conference abstracts cited by relevant review articles. The eligibility of trials was independent of sample size, clinical setting, or date.
resultsA total of 14 studies were eligible for qualitative analysis. The clinical setting was variable among studies, and all utilized an allosteric mTOR inhibitor as either a monotherapy or in combination. Molecular criteria were evaluated in three trials. Among most studies, the prostate-specific antigen level declined during treatment, but often increased shortly thereafter. Partial responses to treatment were minimal, and no complete responses were reported. Two studies exploring therapy with an mTOR inhibitor in combination with bicalutamide resulted in minimal efficacy. Overall, allosteric mTOR inhibition was deemed to be inadequate for the treatment of CRPC.
conclusionPreclinical data suggest that a reciprocal feedback mechanism between PI3K and androgen receptor signaling is a potential mechanism behind the clinical inefficacy of mTOR inhibitors in CRPC, indicating combinatorial targeting of PI3K, mTORC1/2, and the androgen receptor might be more effective. Comprehensive analysis of preclinical data to assess clinical trial targets and efficacy may reduce the number of unproductive trials and identify potentially beneficial combinatorial therapies for resistant disease.
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.