# Ferroptosis—The “Double-Edged Sword” in Cancer: Mechanisms of Tumor Suppression/Resistance and Therapeutic Manipulation

## TL;DR

Ferroptosis, a type of cell death caused by iron overload, can both suppress and promote cancer, making it a complex target for cancer therapy.

## Contribution

This paper reviews the dual role of ferroptosis in cancer and its potential for therapeutic manipulation.

## Key findings

- Ferroptosis can suppress tumor growth by inducing cell death in cancer cells.
- Ferroptosis may also promote tumor progression by negatively affecting anticancer immunity.
- Cancer cells resistant to other forms of cell death can be susceptible to ferroptosis.

## Abstract

Cell death is a process that can occur in cancerous cells in a variety of forms. Ferroptosis is a type of cell death that occurs when there is an overload of iron within the cell, leading to a disruption in vital components of the cellular membrane. In cancer, ferroptosis can play a “double-edged sword” role, where it can be either beneficial or detrimental. There are several factors of ferroptosis that can either promote or prevent cancer from occurring. These factors contribute to pathways that allow it to be studied and manipulated therapeutically for the benefit of treating cancer.

Ferroptosis is a non-apoptotic, iron-dependent form of cell death. The characteristic accumulation of membrane lipid peroxides that occurs is controlled by several different mechanisms including redox homeostasis, the intracellular labile iron pool, and amino acid metabolism. In cancer, ferroptosis can contribute to either tumor progression or tumor suppression. When promoted in cancer cells, ferroptosis plays an innately tumor-suppressive role; however, it can negatively affect anticancer immunity, allowing for tumor growth and progression. Cells that are traditionally known to be resistant to apoptosis and other forms of cell death have demonstrated susceptibility to ferroptosis, making this form of cell death particularly useful in terms of cancer therapeutics. This narrative review will focus on the role of ferroptosis in cancer promotion or prevention and how it can be manipulated therapeutically—whether it be induced or inhibited.