Research programme 03
Quiescence, tumor dormancy and drug resistance
We study when growth arrest protects cancer cells from treatment and when disrupting quiescence creates a therapeutic liability.
Central question
Can the molecular machinery that preserves dormant cancer cells be targeted to prevent relapse or improve the response to cytotoxic and targeted therapies?
Quiescence is essential in normal development, tissue maintenance and stem-cell biology, but cancer cells can use the same state to survive therapy. Dormant cells may remain viable while avoiding drugs that act most strongly on proliferating populations, then later re-enter the cell cycle and drive recurrence.
The laboratory and its collaborators have linked DREAM assembly to ovarian-cancer spheroids, gastrointestinal stromal tumor quiescence and chemotherapy response. These findings support a strategy in which negative growth-control pathways are not viewed only as tumor suppressors, but also as context-dependent survival mechanisms that may be therapeutically disrupted.
Approaches
- Three-dimensional tumor spheroid models
- Drug-response and apoptosis assays
- RNA interference and CRISPR screening
- Quiescence and re-entry measurements
- Combination-therapy studies
- Tumor-dormancy models
Selected work
- A Systematic Analysis of Negative Growth Control Implicates the DREAM Complex in Cancer Cell Dormancy (2017)
- The DREAM complex mediates GIST cell quiescence and is a novel therapeutic target to enhance imatinib-induced apoptosis (2013)
- Progesterone Receptors Promote Quiescence and Ovarian Cancer Cell Phenotypes via DREAM in p53-Mutant Fallopian Tube Models (2021)