ArticlePloS one2016
PI-3K Inhibitors Preferentially Target CD15+ Cancer Stem Cell Population in SHH Driven Medulloblastoma.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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
22 citing papers in PubMed, 31 citations in OpenAlex.
- Cancer Stem Cell Characterization in Olfactory Neuroblastoma Tissue.International forum of allergy & rhinology · 2025Article
- Drivers Underlying Metastasis and Relapse in Medulloblastoma and Targeting Strategies.Cancers · 2024Review
- Current Strategies for Management of Medulloblastoma.Diagnostics (Basel, Switzerland) · 2023Review
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- Current studies and future directions for medulloblastoma: A review from the pacific pediatric neuro-oncology consortium (PNOC) disease working group.Neoplasia (New York, N.Y.) · 2023Review
- NRP1 inhibition modulates radiosensitivity of medulloblastoma by targeting cancer stem cells.Cancer cell international · 2022Article
- Cyclin-Dependent Kinase Inhibitors Function as Potential Immune RegulatorsFrontiers in oncology · 2022Article
- RP11-867G2.8 promotes EMT and chordoma malignant phenotypes by enhancing FUT4 mRNA stability and translation.American journal of cancer research · 2022Article
- Reconciling multiple connectivity scores for drug repurposing.Briefings in bioinformatics · 2021Article
- Tumor Growth in the High Frequency Medulloblastoma Mouse Model Ptch1Frontiers in oncology · 2021Article
- Functional Precision Medicine Identifies New Therapeutic Candidates for Medulloblastoma.Cancer research · 2020Article
- Cellular Stress-Modulating Drugs Can Potentially Be Identified by in Silico Screening with Connectivity Map (CMap).International journal of molecular sciences · 2019Review
- UAB30, A Novel Rexinoid Agonist, Decreases Stemness In Group 3 Medulloblastoma Human Cell Line Xenografts.Translational oncology · 2019Article
- PTEN Tumor-Suppressor: The Dam of Stemness in Cancer.Cancers · 2019Review
- Principles of tumorigenesis and emerging molecular drivers of SHH-activated medulloblastomas.Annals of clinical and translational neurology · 2019Review
- Nilotinib, an approved leukemia drug, inhibits smoothened signaling in Hedgehog-dependent medulloblastoma.PloS one · 2019Article
- Article
- Association of high microvessel αOncotarget · 2017Article
- Article
- Single Agent and Synergistic Activity of the "First-in-Class" Dual PI3K/BRD4 Inhibitor SF1126 with Sorafenib in Hepatocellular Carcinoma.Molecular cancer therapeutics · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Sonic hedgehog (SHH) medulloblastoma (MB) subtype is driven by a proliferative CD15+ tumor propagating cell (TPC), also considered in the literature as a putative cancer stem cell (CSC). Despite considerable research, much of the biology of this TPC remains unknown. We report evidence that phosphatase and tensin homolog (PTEN) and phosphoinositide 3-kinase (PI-3K) play a crucial role in the propagation, survival and potential response to therapy in this CD15+ CSC/TPC-driven malignant disease. Using the ND2-SmoA1 transgenic mouse model for MB, mouse genetics and patient-derived xenografts (PDXs), we demonstrate that the CD15+TPCs are 1) obligately required for SmoA1Tg-driven tumorigenicity 2) regulated by PTEN and PI-3K signaling 3) selectively sensitive to the cytotoxic effects of pan PI-3K inhibitors in vitro and in vivo but resistant to chemotherapy 4) in the SmoA1Tg mouse model are genomically similar to the SHH human MB subgroup. The results provide the first evidence that PTEN plays a role in MB TPC signaling and biology and that PI-3K inhibitors target and suppress the survival and proliferation of cells within the mouse and human CD15+ cancer stem cell compartment. In contrast, CD15+ TPCs are resistant to cisplatinum, temozolomide and the SHH inhibitor, NVP-LDE-225, agents currently used in treatment of medulloblastoma. These studies validate the therapeutic efficacy of pan PI-3K inhibitors in the treatment of CD15+ TPC dependent medulloblastoma and suggest a sequential combination of PI-3K inhibitors and chemotherapy will have augmented efficacy in the treatment of this disease.
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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.