The interplay of oncogenic signaling, oxidative stress and ferroptosis in cancer

Oncogene-induced hyper-proliferation in cancer cells is accompanied by the onset of different stresses, including DNA-replication stress, metabolic stress and oxidative stress. Excessive accumulation of reactive oxygen species (ROS) plays a pivotal and contradictory role in tumor progression. ROS dictates a multitude of cell signaling pathways to facilitate the malignant transformation of tumor cells. In the meantime, oxidative burden in tumor cells mandates reinforcing antioxidant capacity to mitigate detrimental damages. The addiction to oxidative stress and increased iron demands in cancer cells also impinges on the sensitivity of ferroptosis. Targeting redox homeostasis and ferroptosis to overcome drug resistance in cancer treatment has become an attractive research topic. However, the roles of oncogenic signaling in redox regulation and ferroptosis have not been comprehensively discussed. In this review, we summarize current knowledge regarding the interplay between redox regulation and ferroptosis in the context of cancer biology. We emphasize the implication of oncogenic signaling in redox homeostasis and ferroptosis regulation. We also provide an overview of strategies targeting oxidative stress and ferroptosis in cancer treatment.

Automated summary

Oncogene-induced hyper-proliferation in cancer cells leads to different stresses, including DNA-replication stress, metabolic stress, and oxidative stress. The excessive accumulation of reactive oxygen species (ROS) plays a crucial role in tumor progression by influencing cell signaling pathways. Cancer cells also rely on oxidative stress and increased iron demands to affect ferroptosis sensitivity. Targeting redox homeostasis and ferroptosis has become a promising approach to overcome drug resistance in cancer treatment. This review summarizes the current understanding of the interplay between redox regulation, ferroptosis, and oncogenic signaling in cancer biology, and discusses strategies for targeting oxidative stress and ferroptosis in cancer treatment.