Ferroptosis as New Therapeutic Targets in Cancer: from Molecular Mechanisms to Therapeutic Opportunities

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Background

Ferroptosis is a new type of programmed cell death, the process of which is characterized by iron accumulation, extensive production of reactive oxygen species and lipid peroxidation derived from iron metabolism. Emerging evidence has shown that dysregulation of ferroptosis plays an unneglectable role in initiation and progression of cancer by targeting the key regulators such as system Xc-, GPx4, autophagy and iron. Ferroptosis is found to be inhibited in various types of tumors, and induction of ferroptosis can trigger cancer cell death. Notably, ferroptotic inducers may represent a potential strategy for overcoming drug resistance of cancer cell. Although the ferroptosis-based cancer therapy is promising, a lot of progresses have been made to clarify the precise mechanisms underlying the ferroptotic cancer cell death and to identify new targets of ferroptosis for cancer therapy, and there may be various challenges have to be overcome before the ferroptosis-inducing agents can be for clinical use.

Up to now, there are four main classes of ferroptosis-inducing agents in use, including experimental compounds, clinical drugs, nanomedicine, and genes. However, a large-scale profiling studies proved that different cancer cell types have different sensitivities to ferroptotic agents. For instance, non-epithelial cancer cells were more sensitive than epithelial cancer cells, while the underlying mechanism remains largely unknown. Efforts are still needed to identify novel regulatory pathways that control the sensitivity and/or resistance of ferroptosis in cancer. This is important for the discovery of novel therapeutic strategies by inducing ferroptosis to improve the cancer treatment. In addition, a better understanding of the relationship between ferroptosis and different modes of cancer cell death can provide the possibility of combination cancer therapy. More importantly, lack of specific markers of ferroptotic cell death is another urgent problem to be solved in cancer biology, which hinders the evaluation of ferroptosis in vivo and requires further in-depth studies.

In this Research Topic we welcome original research articles, reviews, brief research reports, and clinical trials that specifically dealing with the basic, pre-clinical and clinical studies concerning ferroptosis in cancer, with an emphasis on the role of ferroptosis in cancer development and the response to ferroptosis-related therapy. Subtopics include, but are not limited to
1. Exploring the molecular mechanism and regulatory networks of ferroptosis to provide biomarkers and therapeutic targets for clinical cancer therapy.
2. Understanding the aberrant ferroptosis pathways in different cancer types that regulate ferroptosis sensitivity to aid the design and discovery of ferroptotic agents.
3. Identifying the pharmacological activities and mechanisms of ferroptosis-related anti-tumor drugs supported by animal or clinical data.

Keywords: Ferroptosis, Cancer, Cell Death, Molecular Mechanism, Pharmacology, Cancer Therapy

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