Ferroptosis: An emerging approach for targeting cancer stem cells and drug resistance

Abstract

Resistance to chemotherapeutic agents remains a major challenge in the fierce battle against cancer. Cancer stem cells (CSCs) are a small population of cells in tumors that possesses the ability to self-renew, initiate tumors, and cause resistance to conventional anticancer agents. Targeting this population of cells was proven as a promising approach to eliminate cancer recurrence and improve the clinical outcome. CSCs are less susceptible to death by classical anticancer agents inducing apoptosis. CSCs can be eradicated by ferroptosis, which is a non-apoptotic-regulated mechanism of cell death. The induction of ferroptosis is an attractive strategy to eliminate tumors due to its ability to selectively target aggressive CSCs. The current review critically explored the crosstalk and regulatory pathways controlling ferroptosis, which can selectively induce CSCs death. In addition, successful chemotherapeutic agents that achieve better therapeutic outcomes through the induction of ferroptosis in CSCs were discussed to highlight their promising clinical impact.

Keywords: Autophagy; CD44; Cancer resistance; Cancer stem cells; Ferroptosis; NRF2; YAP/TAZ.