# Unlocking ferroptosis to overcome cancer stem cells-mediated treatment failure and immune evasion

## TL;DR

This review explores how triggering ferroptosis, a form of cell death, can help overcome cancer stem cells that cause treatment failure and immune evasion.

## Contribution

The paper introduces ferroptosis as a novel therapeutic strategy to target cancer stem cells and improve cancer treatment outcomes.

## Key findings

- Ferroptosis is linked to cancer stem cell maintenance and resistance to therapy.
- Non-coding RNAs and metabolic pathways regulate the connection between ferroptosis and stemness.
- Pharmacological approaches, including natural compounds, show potential in inducing ferroptosis in cancer stem cells.

## Abstract

Cancer stem cells (CSCs), a small subset of tumor cells with stem cell - like properties, are central to driving tumorigenesis and metastasis. Growing evidence highlights the importance of ferroptosis in maintaining CSCs, positioning ferroptosis as a promising therapeutic strategy. This review explores the interplay between ferroptosis and CSCs, which drive tumor initiation, therapy resistance, and recurrence. It summarizes the mechanisms of ferroptosis involving iron metabolism, lipid peroxidation, and antioxidant defense. The article highlights how non-coding RNAs, metabolic reprogramming, redox homeostasis, and key signaling pathways interconnect ferroptosis with CSC stemness. Furthermore, it discusses the role of ferroptosis in modulating the tumor immune microenvironment and CSC-mediated immune evasion. The identification of stemness and ferroptosis-related biomarkers offers prognostic value, while pharmacological strategies-including traditional Chinese medicine and natural compounds-show promise in targeting CSCs by inducing ferroptosis. Ultimately, leveraging ferroptosis represents a novel therapeutic approach to eliminate therapy-resistant CSCs and improve cancer treatment outcomes.