How is ferroptosis used in cancer treatment?

Ferroptosis is a form of regulated cell death. It is caused when lipid peroxidation occurs, which is produced through normal metabolic activities. It accumulates to toxic levels causing oxidative damage to cell membranes. 

Under normal circumstances, our cells possess powerful defense mechanisms that help maintain cell survival. When these defense mechanisms get compromised, lipid peroxides accumulate unchecked, building up to toxic levels that damage the integrity of cell membranes and kill cells by ferroptosis. Scientists are exploring ferroptosis as a promising approach in cancer treatment due to its ability to selectively induce cell death in cancer cells. 

Researchers have identified and designed ferroptosis inducers, which are essentially compounds capable of deactivating ferroptosis defense mechanisms, triggering the buildup of toxic cell-damaging lipid peroxides, and causing cells to undergo ferroptosis. Some of these inducers have shown strong efficacy in triggering ferroptosis in suppressing tumor growth in some animal models.

Traditional cancer treatments such as chemotherapy, radiation therapy, and immunotherapy are also capable of inducing ferroptosis in cancer cells. 

One study demonstrated that ionizing radiation, used in radiation therapy, generates reactive oxygen species (ROS) that attack lipid molecules in cancer cells, leading to the production of lipid peroxides, which triggers ferroptosis. 

Another study demonstrated that cytotoxic T cells activated by immunotherapy release interferon-gamma, a cytokine that can weaken the ferroptosis defense in tumor cells, thereby promoting ferroptosis. 

There is growing interest in combining standard cancer treatments such as chemotherapy and radiation therapy with ferroptosis inducers. The goal for researchers is to enhance the effectiveness of cancer treatments by leveraging the ferroptosis pathway to induce more robust cancer cell death.