Ferroptosis in cancer: Mechanisms, therapeutic strategies, and clinical implications

The resistance of cancer cells to existing treatments has become a major challenge for researchers despite advancements in cancer treatment. Studies have shown that this resistance is due to cancer cells evading apoptosis. Moreover, the most common form of cell death induced by chemotherapy and radiotherapy is apoptosis. One of the most essential mechanisms cancer cells escape apoptosis is the excessive expression of tumors' apoptosis inhibitors. Therefore, finding a non-apoptotic pathway that bypasses apoptosis could be a hopeful strategy for cancer treatment. Ferroptosis has been identified as a non-apoptotic and regulated cell death process characterized by the accumulation of lipid peroxides and iron-dependent reactive oxygen species (ROS). Although studies have shown that ferroptosis plays a role in the development of many diseases, including cancer, it also has the potential to decrease resistance to current treatments, such as chemotherapy. Additionally, research has shown that ferroptosis successfully kills cancer cells, such as breast, stem, and lung cancer cells. Therefore, ferroptosis can be identified as a beneficial therapeutic mechanism for cancer treatment. Although ferroptosis has been introduced as an effective treatment path for cancer, its role, along with its therapeutic inducers, in increasing the therapeutic effect has not been investigated. In this review, we aim to introduce ferroptosis, compare it with other cell deaths known so far, and explain its role in cancer treatment. We believe that ferroptosis can be widely used to overcome cancer cells.