Transcriptional regulation of redox pathways

Radiotherapy is a standard care for many cancer patients to achieve local control and to reduce metastatic burden.

While radiation kills tumour cells by inducing DNA damage, it was recently found that ferroptosis is another way of cell killing by radiation. Ferroptosis is an iron-dependent cell death, which is caused by oxidative stresses from fat molecules. However, key pathways involved in the regulation of ferroptosis still need to be investigated.

In our study, we found that the ferroptosis was significantly dependent on MAFF, a protein that regulates antioxidant responses.

We specifically showed that MAFF changed production of reactive oxygen species (ROS) and DNA damage repair during ferroptosis.

While identifying how MAFF regulates ferroptosis and radiation responses by focusing on its target gene pathways, we will also examine whether MAFF is a significant factor in radiation-induced ferroptosis by comparing conventional and FLASH radiotherapy.

FLASH is given at 100-1000 times faster than conventional treatment, which makes it more beneficial by minimizing normal cell killing while having similar radiation effect on tumour.

Therefore, in this study, we will investigate how MAFF-mediated redox pathways regulate ferroptosis, specifically when comparing conventional and FLASH radiotherapy.

Through identification of MAFF-target genes and their role in FLASH treatment, our study will enable us to find a novel therapeutic target to enhance radiation and FLASH outcome.