ArticleJournal of hematology & oncology2019
Identifying and targeting cancer stem cells in leiomyosarcoma: prognostic impact and role to overcome secondary resistance to PI3K/mTOR inhibition.
Article in Journal of hematology & oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 11 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Targeting cancer stem cells by TPA leads to inhibition of refractory sarcoma and extended overall survival.Molecular therapy. Oncology · 2024Article
- Targeted therapy of cancer stem cells: inhibition of mTOR in pre-clinical and clinical research.Cell death & disease · 2024Review
- The mTOR Signaling Pathway and mTOR Inhibitors in Cancer: Next-generation Inhibitors and Approaches.Current molecular medicine · 2024Review
- Cancer Stem Cells in Sarcomas: In Vitro Isolation and Role as Prognostic Markers: A Systematic Review.Cancers · 2023Review
- Conjunctival leiomyosarcoma.American journal of ophthalmology case reports · 2022Article
- Hypoxia increases the expression of stem cell markers in human osteosarcoma cells.Oncology letters · 2021Article
- Review
- Sarcoma treatment in the era of molecular medicine.EMBO molecular medicine · 2020Review
- Cancer Stem Cells in Soft-Tissue Sarcomas.Cells · 2020Review
- Expression of Concern to: Identifying and targeting cancer stem cells in leiomyosarcoma: prognostic impact and role to overcome secondary resistance to PI3K/mTOR inhibition.Journal of hematology & oncology · 2019Article
- Targeting mTOR for cancer therapy.Journal of hematology & oncology · 2019Review
Corrections and comments
- Expression of concern · 2019-11-22Concerns/Issues about Authorship/Affiliation · Copyright Claims ·
- Expression of concern
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLeiomyosarcoma (LMS) is one of the most frequent soft tissue sarcoma subtypes and is characterized by a consistent deregulation of the PI3K/mTOR pathway. Cancer stem cells (CSCs) have been poorly studied in soft tissue sarcomas. In this study, we aimed to evaluate the association between CSCs, the outcome of LMS patients, and the resistance to PI3K/mTOR pathway inhibition.
methodsWe investigated the relationships between aldehyde dehydrogenase 1 (ALDH1) expression, a cancer stem cell marker, and the outcome of LMS patients in two independent cohorts. We assessed the impact of CSCs in resistance to PI3K/mTOR pathway inhibition using LMS cell lines, a xenograft mouse model, and human tumor samples.
resultsWe found that enhanced ALDH1 activity is a hallmark of LMS stem cells and is an independent prognostic factor. We also identified that secondary resistance to PI3K/mTOR pathway inhibition was associated with the expansion of LMS CSCs. Interestingly, we found that EZH2 inhibition, a catalytic component of polycomb repressive complex which plays a critical role in stem cell maintenance, restored sensitivity to PI3K/mTOR pathway inhibition. Importantly, we confirmed the clinical relevance of our findings by analyzing tumor samples from patients who showed secondary resistance after treatment with a PI3Kα inhibitor.
conclusionsAltogether, our findings suggest that CSCs have a strong impact on the outcome of patients with LMS and that combining PI3K/mTOR and EZH2 inhibitors may represent a promising strategy in this setting.
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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.