ArticleThe Journal of clinical investigation2023
Metixene is an incomplete autophagy inducer in preclinical models of metastatic cancer and brain metastases.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses 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.
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Who cites it
10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.
- Repurposing neurological drugs for brain cancer therapeutics: A systematic approach to identify charged molecules for affinity-based local drug delivery systems.International journal of pharmaceutics · 2025Pooled it
- New trends in brain tumor immunity with the opportunities of lymph nodes targeted drug delivery.Journal of nanobiotechnology · 2023Pooled it
- Microglial TBK1 Signaling Promotes Breast Cancer Brain Metastasis.Cancer research · 2026Article
- Immunosuppressive mechanisms and therapeutic interventions shaping glioblastoma immunity.Nature cancer · 2026Review
- Exploring Autophagy Inducing Molecules: Targeting Diverse Pathways in Alzheimer's Disease Management.Medicinal research reviews · 2026Review
- Insight into the Regulation of NDRG1 Expression.International journal of molecular sciences · 2025Review
- Anti-Cancer Strategy Based on Changes in the Role of Autophagy Depending on the Survival Environment and Tumorigenesis Stages.Molecules (Basel, Switzerland) · 2024Review
- Immunomodulatory signalling networks in glioblastoma multiforme: a comprehensive review of therapeutic approaches.Human cell · 2024Review
- Therapeutic cell-based vaccines for glioblastoma multiforme.Medical oncology (Northwood, London, England) · 2023Review
- Jianpi Jiedu Recipe Inhibits Proliferation through Reactive Oxygen Species-Induced Incomplete Autophagy and Reduces PD-L1 Expression in Colon Cancer.Integrative cancer therapiesArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 2 institutions in 2 countries.
Funding
Abstract
A paucity of chemotherapeutic options for metastatic brain cancer limits patient survival and portends poor clinical outcomes. Using a CNS small-molecule inhibitor library of 320 agents known to be blood-brain barrier permeable and approved by the FDA, we interrogated breast cancer brain metastasis vulnerabilities to identify an effective agent. Metixene, an antiparkinsonian drug, was identified as a top therapeutic agent that was capable of decreasing cellular viability and inducing cell death across different metastatic breast cancer subtypes. This agent significantly reduced mammary tumor size in orthotopic xenograft assays and improved survival in an intracardiac model of multiorgan site metastases. Metixene further extended survival in mice bearing intracranial xenografts and in an intracarotid mouse model of multiple brain metastases. Functional analysis revealed that metixene induced incomplete autophagy through N-Myc downstream regulated 1 (NDRG1) phosphorylation, thereby leading to caspase-mediated apoptosis in both primary and brain-metastatic cells, regardless of cancer subtype or origin. CRISPR/Cas9 KO of NDRG1 led to autophagy completion and reversal of the metixene apoptotic effect. Metixene is a promising therapeutic agent against metastatic brain cancer, with minimal reported side effects in humans, which merits consideration for clinical translation.
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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.