Title :

Evofosfamide Is Effective against Pediatric Aggressive Glioma Cell Lines in Hypoxic Conditions and Potentiates the Effect of Cytotoxic Chemotherapy and Ionizing Radiations

Author(s) :

Bailleul, Quentin [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Navarin, Pauline [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Arcicasa, Mélanie [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Bal-Mahieu, Christine [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Carcaboso, Angel Montero [Auteur]
Le Bourhis, Xuefen [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Furlan, Alessandro [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Meignan, Samuel [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] [UNICANCER/Lille]
Leblond, Pierre [Auteur]
Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] [IHOPe]

Journal title :

Cancers

Pages :

1804

Publisher :

MDPI

Publication date :

2021

ISSN :

2072-6694

English keyword(s) :

high-grade glioma
Evofosfamide
hypoxia
radiotherapy
child
DIPG

HAL domain(s) :

Sciences du Vivant [q-bio]/Cancer
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Pédiatrie
Sciences du Vivant [q-bio]/Neurosciences [q-bio.NC]/Neurobiologie
Sciences du Vivant [q-bio]/Sciences pharmaceutiques/Pharmacologie

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL