{"doi":"10.1158/1541-7786.c.6544959","title":"Data from Transcriptomic Analysis of Diffuse Intrinsic Pontine Glioma (DIPG) Identifies a Targetable ALDH-Positive Subset of Highly Tumorigenic Cancer Stem-like Cells","abstract":"<div>Abstract<p>Understanding the cancer stem cell (CSC) landscape in diffuse intrinsic pontine glioma (DIPG) is desperately needed to address treatment resistance and identify novel therapeutic approaches. Patient-derived DIPG cells demonstrated heterogeneous expression of aldehyde dehydrogenase (ALDH) and CD133 by flow cytometry. Transcriptome-level characterization identified elevated mRNA levels of <i>MYC, E2F</i>, DNA damage repair (DDR) genes, glycolytic metabolism, and mTOR signaling in ALDH<sup>+</sup> compared with ALDH<sup>−</sup>, supporting a stem-like phenotype and indicating a druggable target. ALDH<sup>+</sup> cells demonstrated increased proliferation, neurosphere formation, and initiated tumors that resulted in decreased survival when orthotopically implanted. Pharmacologic MAPK/PI3K/mTOR targeting downregulated <i>MYC, E2F</i>, and <i>DDR</i> mRNAs and reduced glycolytic metabolism. <i>In vivo</i> PI3K/mTOR targeting inhibited tumor growth in both flank and an ALDH<sup>+</sup> orthotopic tumor model likely by reducing cancer stemness. In summary, we describe existence of ALDH<sup>+</sup> DIPGs with proliferative properties due to increased metabolism, which may be regulated by the microenvironment and likely contributing to drug resistance and tumor recurrence.</p>Implications:<p>Characterization of ALDH<sup>+</sup> DIPGs coupled with targeting MAPK/PI3K/mTOR signaling provides an impetus for molecularly targeted therapy aimed at addressing the CSC phenotype in DIPG.</p></div>","journal":null,"year":2023,"id":406091,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8989,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":497994,"name":"Sarah F. Ferris","orcid":"0009-0009-3389-7911","position":1,"is_corresponding":false},{"id":497995,"name":"April A. Apfelbaum","orcid":"0000-0002-3551-4429","position":2,"is_corresponding":false},{"id":225400,"name":"Carlos E. Espinoza","orcid":"0009-0000-0460-1514","position":3,"is_corresponding":false},{"id":397023,"name":"Ranjit K. Mehta","orcid":"0000-0002-2735-1682","position":4,"is_corresponding":false},{"id":498611,"name":"Karamoja Monchamp","orcid":null,"position":5,"is_corresponding":false},{"id":225395,"name":"Veerin R. Sirihorachai","orcid":"0000-0003-4992-6499","position":6,"is_corresponding":false},{"id":260368,"name":"Karan Bedi","orcid":"0000-0002-7843-738X","position":7,"is_corresponding":false},{"id":260370,"name":"Mats Ljungman","orcid":"0000-0003-1553-6695","position":8,"is_corresponding":false},{"id":433954,"name":"Stefanie Galbán","orcid":"0000-0001-5012-7614","position":9,"is_corresponding":false},{"id":433952,"name":"Rachel K. Surowiec","orcid":"0000-0001-7614-4412","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:59.152593Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}