title: Therapeutic targets in subependymoma.
abstract: Subependymomas are usually treated with surgical resection; however, no standard, defined alternative medical therapy is recommended for patients who are not surgical candidates, owing to a paucity of molecular, immunological, and genetic characterization. To address this, an ex vivo functional analysis of the immune microenvironment in subependymoma was conducted, a subependymoma cytokine/chemokine microarray was constructed for the evaluation of operational immune and molecular pathways, and a subependymoma cell line was derived and used to test a variety of cytotoxic agents that target operational pathways identified in subependymoma. We found that immune effectors are detectable within the microenvironment of subependymoma; however, marked immune suppression is not observed. The subependymoma tissue microarrays demonstrated tumor expression of p53, MDM2, HIF-1α, topoisomerase II-β, p-STAT3, and nucleolin, but not EGFRvIII, EphA2, IL-13RA2, CMV, CTLA-4, FoxP3, PD-1, PD-L1, EGFR, PDGF-α, PDGF-β, PDGFR-α, PDGFR-β, PTEN, IGFBP2, PI3K, MDM4, IDH1, mTOR, or Jak2. A topoisomerase inhibitor (WP744, IC50=0.83 μM) and a p-STAT3/HIF-1α inhibitor (WP1066, IC50=3.15 μM) demonstrated a growth inhibition of the subependymoma cell proliferation. Cumulatively, these data suggest that those agents that interfere with oncogenes operational in subependymoma may have clinical impact.
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Ling-Yuan
authors.initials: LY
authors.lastname: Kong
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Ali S
authors.initials: AS
authors.lastname: Haider
authors.affiliation: Department of Neurosurgery, Houston Methodist, Houston, TX 77030, United States.
authors.forename: Brandon D
authors.initials: BD
authors.lastname: Liebelt
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Ling
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Conrad
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Fuller
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Levine
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Priebe
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.
authors.forename: Raymond
authors.initials: R
authors.lastname: Sawaya
authors.affiliation: Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States. Electronic address: aheimber@mdanderson.org.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Heimberger
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018315:Glioma, Subependymal / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D046888:Tissue Array Analysis; D020032:Tyrphostins / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D009363:Neoplasm Proteins; D011725:Pyridines; D020032:Tyrphostins; C519885:WP1066
keywords: Ependymoma; Immunotherapy; Noninvasive; Subependymoma