Targeting Cancer Cell Dormancy and Reactivation: Mechanisms of Latency and Relapse in Metastatic Disease
Cancer dormancy represents a major clinical challenge, as dormant disseminated tumour cells (DTCs) can persist for years after primary treatment and later reactivate to form incurable metastases. Understanding and targeting the biological mechanisms that regulate dormancy, and its reversal is key to preventing metastatic relapse in breast and other cancers.
This project will investigate the molecular pathways that control the induction, maintenance, and escape from dormancy, using established dormancy models, 3D co-culture systems, and in vivo assays. Drawing on recent advances from our lab (https://jeccr.biomedcentral.com/articles/10.1186/s13046-023-02663-8) and others, we will focus on:
- Cell-intrinsic regulators of dormancy, including cell cycle arrest, quiescence, and autophagy
- Dormancy-inducing signals from the tumour microenvironment, including TGF-β, integrin, BMP and other pathways
- Identification of key molecular switches that trigger reactivation from dormancy (various candidates have been identified)
- Functional validation of candidate genes or druggable targets that sustain latency or drive relapse
We will use advanced techniques such as time-lapse live-cell imaging, transcriptomics, functional genomics (CRISPR screens), and patient-derived organoid models to track and manipulate dormant cell behaviour in real time.