Targeting ferroptosis in cancer therapy: Mechanisms, strategies, and clinical applications
Zhangshuai Dai, Jinyi Liu, Liyi Zeng, Kunyu Shi, Xueting Peng, Zhenyi Jin, Runhui Zheng, Chengwu Zeng
Abstract
Programmed cell death (PCD) is a fundamental biological process that plays a critical role in maintaining cellular homeostasis and modulating the effectiveness of cancer therapies. Among the various forms of PCD, ferroptosis has recently attracted considerable attention as a promising strategy to overcome therapeutic resistance, which often limits the success of conventional treatments such as chemotherapy. This review delves into the molecular mechanisms underlying the susceptibility of different cell types to ferroptosis, highlighting the pathways involved and the diverse cellular responses triggered by therapeutic interventions. We also explore various strategies to enhance ferroptosis sensitivity in cancer cells, including the manipulation of cell therapy, transcription factors, regulatory genes, ion homeostasis, organelle functions, and the extracellular environment. Additionally, we examine current and emerging therapeutic agents targeting ferroptosis, discussing their clinical potential and prospects for integration into cancer treatment regimens. By reviewing both the underlying mechanisms and therapeutic approaches related to ferroptosis, this article aims to provide valuable insights into how targeting this unique form of cell death may help address tumor resistance and improve patient outcomes.