The impact of chronological ageing on breast tumour initiation (360G-Wellcome-337959_Z_25_Z)

Breast cancer is the most common cancer in women worldwide, and its molecular and cellular heterogeneity at late stages remains a major barrier to curative treatment. This highlights the importance of developing approaches of early detection and intervening prophylactically to prevent tumour development. A key obstacle lies in our poor understanding of the events that drive tumour initiation. Ageing is the strongest risk factor for breast cancer, yet the biological mechanisms by which ageing is involved in early breast tumourigenesis are largely unknown. This project aims to reveal the impact of chronological ageing on tumour initiation and mammary tissue state responses, and to explore whether therapeutic interventions aimed at rejuvenating tissue could impact breast tumour initiation. This project specifically aims to: 1) map the impact of chronological ageing on tissue state response during breast tumour initiation 2) investigate the impact of chronological ageing on clonal dynamics during breast tumour initiation 3) assess the impact of chronological ageing on the mutational landscape during breast tumour initiation 4) discover how therapeutic rejuvenation could impact breast tumour initiation. In an ageing population, this knowledge could provide the foundation for improving early detection strategies and developing new approaches for preventing breast cancer.