Hadrontherapy and PARP inhibitors effects on chondrosarcoma cancer stem cells - Archive ouverte HAL Accéder directement au contenu
Poster De Conférence Année : 2023

Hadrontherapy and PARP inhibitors effects on chondrosarcoma cancer stem cells

Résumé

Hypoxia can lead to resistance of conventional X-rays treatment by the absence of oxygen, essential for the formation of Reactive Oxygen Species (ROS) associated with cellular toxicity. Hypoxia is also related to a possible stabilization of subpopulation of Cancer Stem Cells (CSCs) described as having increased DNA repair systems [1,2]. In order to overcome cell resistance, innovative therapeutic strategies are proposed, for instance hadrontherapy (proton and carbon ions therapy) and targeted radiosensitizing molecules, such as PARP inhibitors, whose effects have been previously described in the context of chondrosarcoma [3]. For this study, the impact of the different irradiations qualities (X-rays, protons and carbon ions) in association with the PARP inhibitor olaparib, under low (1%) and high (20%) oxygen conditions were analyzed on 2 chondrosarcoma cell lines with different mutational status regarding IDH1 : JJ012 (mutated) and Oums27 (wt). Cell survival was evaluated by clonogenic assays and the impact of treatments on CSC subpopulation was studied using an ALDH activity test by flow cytometry and RTqPCR. According to our first experiments, hypoxia increased cellular resistance to X-rays; this effect is less evident with protons and carbon ions. PARP inhibitor radiosensitized against X-rays, the effect was lower with carbon ions. These preliminary results showed that CSC sub-population seemed more sensitive to carbon ions than X-rays, in association with PARP inhibitor. Taken together, these results suggest that hadrontherapy in association with PARP inhibitor could be a good alternative for overcome the chondrosarcoma radioresistance, depending on the mutation status and oxygen growth conditions of the cells. References 1. Gilbert, A. et al. Cancers 2023, 15, 1962, doi:10.3390/cancers15071962. 2. Vares, G. et al. Radiotherapy and Oncology 2020, 150, 253-261, doi:10.1016/j.radonc.2020.07.034. 3. Césaire, M. et al. Journal of Bone Oncology 2019, 17, 100246, doi:10.1016/j.jbo.2019.100246.
Fichier non déposé

Dates et versions

hal-04217091 , version 1 (25-09-2023)

Identifiants

  • HAL Id : hal-04217091 , version 1

Citer

Antoine Gilbert, Kevin Commenchail, Samuel Valable, François Chevalier. Hadrontherapy and PARP inhibitors effects on chondrosarcoma cancer stem cells. ICRR 2023, Aug 2023, Montréal Québec, Canada. ⟨hal-04217091⟩
30 Consultations
0 Téléchargements

Partager

Gmail Facebook X LinkedIn More