Trial reportInvestigational new drugs2018
A phase II study of the dual mTOR inhibitor MLN0128 in patients with metastatic castration resistant prostate cancer.
Trial report in Investigational new drugs, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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
51 citing papers in PubMed, 88 citations in OpenAlex.
- PKA signaling modulates PRMT5/hnRNP A1-mediated IRES translation and dictates responses to mTOR inhibition in glioblastoma.Journal of neuro-oncology · 2026Article
- mTORC1 activity suppresses ferroptosis through a SCARB1-dependent HDL-tocopherol uptake pathway.Molecular cell · 2026Article
- The 4E-BPs as Translational Regulators in Neurological Disorders: Molecular Mechanisms and Therapeutic Potential.Molecular neurobiology · 2025Review
- Caloric Restriction Enhances the Efficacy of Antiandrogen Therapy in Prostate Cancer by Inhibiting Androgen Receptor Translation.Cancer research · 2025Article
- A small-molecule anti-cancer drug for long-acting lysosomal damage.Acta pharmaceutica Sinica. B · 2025Article
- Targeting MYC: Multidimensional regulation and therapeutic strategies in oncology.Genes & diseases · 2025Review
- Silencing APLNR enhances the radiosensitivity of prostate cancer by modulating the PI3K/AKT/mTOR signaling pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- mTORC1, the maestro of cell metabolism and growth.Genes & development · 2025Review
- Lessons learned from 20 years of preclinical testing in pediatric cancers.Pharmacology & therapeutics · 2024Review
- Identification of an anaplastic subtype of prostate cancer amenable to therapies targeting SP1 or translation elongation.Science advances · 2024Article
- Dual targeting of the androgen receptor and PI3K/AKT/mTOR pathways in prostate cancer models improves antitumor efficacy and promotes cell apoptosis.Molecular oncology · 2024Article
- Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.Signal transduction and targeted therapy · 2023Review
- Recent advances and future perspectives in the therapeutics of prostate cancer.Experimental hematology & oncology · 2023Article
- The Molecular Biology of Prostate Cancer Stem Cells: From the Past to the Future.International journal of molecular sciences · 2023Review
- The Role of ERα and ERβ in Castration-Resistant Prostate Cancer and Current Therapeutic Approaches.Biomedicines · 2023Review
- Cancer immune evasion through KRAS and PD-L1 and potential therapeutic interventions.Cell communication and signaling : CCS · 2023Review
- Therapeutic targeting of histone lysine demethylase KDM4B blocks the growth of castration-resistant prostate cancer.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- LINC01088/miR-22/CDC6 Axis Regulates Prostate Cancer Progression by Activating the PI3K/AKT Pathway.Mediators of inflammation · 2023Article
- Dual contribution of the mTOR pathway and of the metabolism of amino acids in prostate cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Genomic signature of MTOR could be an immunogenicity marker in human colorectal cancer.BMC cancer · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Background MLN0128 is a first-in-class, dual mTOR inhibitor with potential to outperform standard rapalogs through inhibition of TORC1 and TORC2. This phase II study was designed to assess antitumor activity of MLN0128 in metastatic castration-resistant prostate cancer (mCRPC). Methods Eligible patients had mCRPC previously treated with abiraterone acetate and/or enzalutamide. Five patients started MLN0128 at 5 mg once daily, subsequently dose reduced to 4 mg because of toxicity. Four subsequent patients started MLN0128 at 4 mg daily. Primary endpoint was progression-free survival at 6 months. Results Nine patients were enrolled and median time on treatment was 11 weeks (range: 3-30). Best response was stable disease. All patients had a rise in PSA on treatment, with a median 159% increase from baseline (range: 12-620%). Median baseline circulating tumor cell count was 1 cell/mL (range: 0-40); none had a decrease in cell count posttreatment. Grade ≤ 2 adverse events included fatigue, anorexia, and rash. The most common serious adverse events were grade 3 dyspnea and maculopapular rash. Eight patients discontinued treatment early because of radiographic progression (n = 1), grade 3 toxicity (n = 5), or investigator discretion (n = 2). Four patients had immediate PSA decline following drug discontinuation, suggesting MLN0128 could cause compensatory increase of androgen receptor (AR) activity. Correlative studies of pretreatment and posttreatment biopsy specimens revealed limited inhibition of AKT phosphorylation, 4EBP1 phosphorylation, and eIF4E activity. Conclusions Clinical efficacy of MLN0128 in mCRPC was limited likely due to dose reductions secondary to toxicity, PSA kinetics suggesting AR activation resulting from mTOR inhibition, and poor inhibition of mTOR signaling targets.
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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.