Targeting breast cancer metabolism to inhibit irradiation-induced migration and induce radiosensitization
(2024)
Files
PDFTHESISFINALMANUSCRIPTFORPRINTNOV12JR.pdf
Embargo Access until 2027-11-12 - Adobe PDF
- 15.1 MB
Details
- Authors
- Supervisors
- Sonveaux, Pierre
- Abstract
- Radiotherapy is a gold standard treatment option for women with breast cancer. However, many mechanisms surrounding radiotherapy remain to be elucidated. This doctoral thesis sheds light on two primary radiotherapeutic concepts in the context of mitochondrial metabolism, using human breast cancer cell lines as working models. Firstly, we demonstrate that subclinical doses of radiation trigger breast cancer migration through a mitochondrial ROS-induced gene program, and by designing a novel mitochondrial-targeted catalase we discover that mitochondrial hydrogen peroxide is a key second messenger mediating subclinical radiation induced breast cancer cell migration. Secondly, this work explores the use of MitoQ as a novel radiosensitizing agent, capable of effectively decreasing in vitro and in vivo breast cancer cell hypoxia via a reduction in mitochondrial respiration. Altogether, this research places mitochondrial metabolism at the forefront of breast cancer cell response to irradiation insult and offers therapeutic insights for effective radiosensitization.
- Affiliations
Citations
Rondeau, J. (2024). Targeting breast cancer metabolism to inhibit irradiation-induced migration and induce radiosensitization. https://hdl.handle.net/2078.5/234731