P2X7 receptor isoform B is a key drug resistance mediator for neuroblastoma

Vanessa Fernandes Arnaud-Sampaio; Carolina Adriane Bento; Talita Glaser; Elena Adinolfi; Henning Ulrich; Claudiana Lameu

doi:10.3389/fonc.2022.966404

P2X7 receptor isoform B is a key drug resistance mediator for neuroblastoma

Front Oncol. 2022 Aug 25:12:966404. doi: 10.3389/fonc.2022.966404. eCollection 2022.

Authors

Vanessa Fernandes Arnaud-Sampaio¹, Carolina Adriane Bento¹, Talita Glaser¹, Elena Adinolfi², Henning Ulrich¹, Claudiana Lameu¹

Affiliations

¹ Biochemistry Department, Institute of Chemistry, University of Sao Paulo, Sao Paulo, SP, Brazil.
² Section of Experimental Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.

Abstract

Drug resistance is a major challenge for all oncological treatments that involve the use of cytotoxic agents. Recent therapeutic alternatives cannot circumvent the ability of cancer cells to adapt or alter the natural selection of resistant cells, so the problem persists. In neuroblastoma, recurrence can occur in up to 50% of high-risk patients. Therefore, the identification of novel therapeutic targets capable of modulating survival or death following classical antitumor interventions is crucial to address this problem. In this study, we investigated the role of the P2X7 receptor in chemoresistance. Here, we elucidated the contributions of P2X7 receptor A and B isoforms to neuroblastoma chemoresistance, demonstrating that the B isoform favors resistance through a combination of mechanisms involving drug efflux via MRP-type transporters, resistance to retinoids, retaining cells in a stem-like phenotype, suppression of autophagy, and EMT induction, while the A isoform has opposite and complementary roles.

Keywords: P2X7 receptor isoforms; autophagy; cancer; cancer stem cells; chemoresistance; childhood cancer; drug efflux; epithelial-mesenchymal transition.