Eradicate dormant cancer cells: a programme to wake and kill or lock asleep disseminated cells
Many relapses come from cancer cells that hid dormant for years. Find drugs that either force them awake so chemotherapy kills them, or keep them asleep for life.
Disseminated tumour cells in bone marrow and other niches survive therapy in a quiescent state maintained by niche signals (TGF-beta 2, BMP, NR2F1, autophagy) and cause late relapse in breast, prostate and melanoma. Preclinical work shows both awakening strategies (sensitising to chemotherapy) and dormancy-enforcing strategies (NR2F1 agonists, 5-azacytidine plus retinoic acid, CDK4/6 inhibitors) can reduce metastasis. The proposal is a coordinated programme: standardised dormant-cell models, biomarkers of dormancy burden in patients (bone marrow and ctDNA), and adjuvant trials of dormancy-directed therapy in patients with detected disseminated cells.
- Dormant cells and minimal residual disease · After a 'successful' treatment, cells can sleep for years then relapse. We can barely detect them and cannot target them.
- Metastasis is understood least and studied last · Metastasis causes about nine in ten cancer deaths but gets a small fraction of research money and almost no trials of its own.