Understanding AKT-mediated chemoresistance: the relationship between ion channels and AKT activation

TL;DR

This paper reviews how AKT activation influences chemoresistance in cancer, highlighting the roles of ion channels and downstream targets like c-myc and p53, and proposing potential therapeutic targets.

Contribution

It introduces the potential link between ion channels, AKT activation, and ABC transporter-mediated chemoresistance in cancer.

Findings

AKT influences chemoresistance via c-myc and p53 pathways.

Ion channels like Orai and TRPC may regulate AKT activation.

Targeting ion channels could offer new cancer therapies.

Abstract

Overcoming chemoresistance is a challenge for multiple chemotherapeutics agents like cisplatin. ABC transporters such as MDR1 or MRPs and PI3K/AKT pathway have been proposed as actors of chemoresistance in several cancers. In this review we describe two downstream targets of Akt: c-myc and p53 in the chemoresistance. We suggest a potential link between p53, c-myc and ABC transporters expression. Consequently a link between Akt and ABC transporters-mediated chemoresistance may exist. Finally we show that Akt activation may be Orai-dependent and/or TRPC-dependent, suggesting that these ion channels could constitute a therapeutic target in cancer.