Ferroptosis, necroptosis, and pyroptosis in cancer: Crucial cell death types in radiotherapy and post-radiotherapy immune activation.

Abstract

Tumor cell death and antitumor immune activation induced by radiotherapy are extensively well-studied. While radiotherapy is believed to mainly induce tumor cell necrosis and apoptosis, recent studies have shown that it can also induce ferroptosis, necroptosis, and pyroptosis in tumor cells. However, studies on the role of ferroptosis, necroptosis, and pyroptosis in radiotherapy and post-radiotherapy immune activation are limited. In this review, we summarize the comprehensive literature on the molecular mechanisms and more recent research progress related to radiotherapy-induced ferroptosis, necroptosis, and pyroptosis in tumor cells. Further, we discuss the role of tumor cells undergoing these types of cell death in immune activation after radiotherapy. In addition, we highlight some unresolved questions on the association of radiotherapy with ferroptosis, necroptosis, and pyroptosis. This review can improve our current understanding of the relationship between radiotherapy and different cell death pathways and provide a theoretical framework to improve the therapeutic effect of tumor radiotherapy in the future.