Decoding the spatiotemporal characteristics of ferroptosis: reshaping tumour therapeutic strategies

The resistance to treatment and the high chance of death associated with cancer still remain key problems that need breakthrough in biology and medicine. Ferroptosis is a newly discovered form of regulated cell death that is driven by iron and lipid peroxidation. Research reveals that ferroptosis plays an important role in tumour initiation, progression, and treatment. Furthermore, this process is mediated by distinct and dynamic molecular mechanisms. All of this information about the importance of ferroptosis will provide new targets and opportunities for cancer therapies. Cross-talk with other cell death pathways (e.g. apoptosis, necroptosis, autophagy) can modulate ferroptosis, and in some contexts these interactions may inhibit ferroptosis execution or activate adaptive survival responses in tumour cells. Ferroptosis has an initiation stage, a subsequent execution stage, and lastly a termination stage. Moreover, the sensitivity and response mechanisms of tumour cells to ferroptosis have significant differences in the early stage, progressive stage, metastatic stage, recurrent stage, etc. Due to the heterogeneous microenvironmental characteristics of hypoxic regions, immune-infiltrated regions and fibrotic regions in the spatial area of the tumour microenvironment (TME), these regions dynamically interact with ferroptosis. At present, strategies based on ferroptosis for tumour therapy have shown great promise. The use of advanced stimulus-responsive nanotechnology with classical ferroptosis inducers will enable the precise delivery and slow release of these inducers to enhance therapeutic efficacy and minimise damage to normal tissues. Nonetheless, several hurdles remain for clinical translation. A detailed examination of the complex regulatory networks in the TME, the development of scalable manufacturing processes for nanosystems, and the identification of non-invasive biomarkers to monitor the efficacy of ferroptosis are critical breakthrough points in the translation of ferroptosis-based therapy from bench to bedside.