{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T04:07:16Z","timestamp":1793074036418,"version":"4.5.0"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T00:00:00Z","timestamp":1617926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Hypoxia is a hallmark of many solid tumors and is associated with resistance to anticancer treatments. Hypoxia-activated prodrugs (HAPs) were developed to target the hypoxic regions of these tumors. Among 2nd generation HAPs, Evofosfamide (Evo, also known as TH-302) exhibits preclinical and clinical activities against adult glioblastoma. In this study, we evaluated its potential in the field of pediatric neuro-oncology. We assessed the efficacy of Evo in vitro as a single drug, or in combination with SN38, doxorubicin, and etoposide, against three pediatric high-grade glioma (pHGG) and three diffuse intrinsic pontine glioma (DIPG) cell lines under hypoxic conditions. We also investigated radio-sensitizing effects using clonogenic assays. Evo inhibited the growth of all cell lines, mainly under hypoxia. We also highlighted a significant synergism between Evo and doxorubicin, SN38, or etoposide. Finally, Evo radio-sensitized the pHGG cell line tested, both with fractionated and single-dose irradiation schedules. Altogether, we report here the first preclinical proof of evidence about Evofosfamide efficiency against hypoxic pHGG and DIPG cells. Since such tumors are highly hypoxic, and Evo potentiates the effect of ionizing radiation and chemotherapy, it appears as a promising therapeutic strategy for children with brain tumors.<\/jats:p>","DOI":"10.3390\/cancers13081804","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T10:05:21Z","timestamp":1617962721000},"page":"1804","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Evofosfamide Is Effective against Pediatric Aggressive Glioma Cell Lines in Hypoxic Conditions and Potentiates the Effect of Cytotoxic Chemotherapy and Ionizing Radiations"],"prefix":"10.3390","volume":"13","author":[{"given":"Quentin","family":"Bailleul","sequence":"first","affiliation":[{"name":"Unit\u00e9 Tumorigen\u00e8se et R\u00e9sistance aux Traitements, Centre Oscar Lambret, 59000 Lille, France"},{"name":"UMR9020-U1277\u2014CANTHER\u2014Cancer Heterogeneity Plasticity and Resistance to Therapies, CHU Lille, University Lille, CNRS, Inserm, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Navarin","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Tumorigen\u00e8se et R\u00e9sistance aux Traitements, Centre Oscar Lambret, 59000 Lille, France"},{"name":"Service d\u2019Onco-H\u00e9matologie P\u00e9diatrique, CHU Lille, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Arcicasa","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Tumorigen\u00e8se et R\u00e9sistance aux Traitements, Centre Oscar Lambret, 59000 Lille, France"},{"name":"UMR9020-U1277\u2014CANTHER\u2014Cancer Heterogeneity Plasticity and Resistance to Therapies, CHU Lille, University Lille, CNRS, Inserm, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bal-Mahieu","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Tumorigen\u00e8se et R\u00e9sistance aux Traitements, Centre Oscar Lambret, 59000 Lille, France"},{"name":"UMR9020-U1277\u2014CANTHER\u2014Cancer Heterogeneity Plasticity and Resistance to Therapies, CHU Lille, University Lille, CNRS, Inserm, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8485-426X","authenticated-orcid":false,"given":"Angel Montero","family":"Carcaboso","sequence":"additional","affiliation":[{"name":"Institut de Recerca Sant Joan de Deu, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6790-6358","authenticated-orcid":false,"given":"Xuefen","family":"Le Bourhis","sequence":"additional","affiliation":[{"name":"UMR9020-U1277\u2014CANTHER\u2014Cancer Heterogeneity Plasticity and Resistance to Therapies, CHU Lille, University Lille, CNRS, Inserm, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Furlan","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Tumorigen\u00e8se et R\u00e9sistance aux Traitements, Centre Oscar Lambret, 59000 Lille, France"},{"name":"UMR9020-U1277\u2014CANTHER\u2014Cancer Heterogeneity Plasticity and Resistance to Therapies, CHU Lille, University Lille, CNRS, Inserm, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9386-7978","authenticated-orcid":false,"given":"Samuel","family":"Meignan","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Tumorigen\u00e8se et R\u00e9sistance aux Traitements, Centre Oscar Lambret, 59000 Lille, France"},{"name":"UMR9020-U1277\u2014CANTHER\u2014Cancer Heterogeneity Plasticity and Resistance to Therapies, CHU Lille, University Lille, CNRS, Inserm, 59000 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Leblond","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Canc\u00e9rologie P\u00e9diatrique, Institut D\u2019h\u00e9matologie et D\u2019oncologie P\u00e9diatrique, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"v1","DOI":"10.1093\/neuonc\/noz150","article-title":"CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012\u20132016","volume":"21","author":"Ostrom","year":"2019","journal-title":"Neuro. 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