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.
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not linked directly; found by shared links- IdeaKeep dormant cells asleep instead of trying to kill them
Shares Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET), Metastasis is understood least and studied last, Dormant cells and minimal residual disease, Minimal / molecular residual disease (MRD).
- IdeaBlunt the inflammation that wakes sleeping cancer cells
Shares Metastasis is understood least and studied last, Dormant cells and minimal residual disease, Minimal / molecular residual disease (MRD), HR-positive / HER2-negative breast cancer.
- IdeaFlush dormant cells out of bone marrow, then kill them
Shares Metastasis is understood least and studied last, Dormant cells and minimal residual disease, Minimal / molecular residual disease (MRD), HR-positive / HER2-negative breast cancer.
- IdeaStarve the survivors: target the energy pathway drug-tolerant cells switch to
Shares Dormant cells and minimal residual disease, Minimal / molecular residual disease (MRD), Melanoma.
- IdeaCirculating tumour cell clearance as the phase 2 gate for anti-metastatic drugs
Shares Metastasis is understood least and studied last, Minimal / molecular residual disease (MRD), Prostate cancer, HR-positive / HER2-negative breast cancer.
- IdeaA blood test for the pre-metastatic niche
Shares Metastasis is understood least and studied last, Dormant cells and minimal residual disease, HR-positive / HER2-negative breast cancer.
- PersonWilliam G. Nelson
Shares Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET), Prostate cancer.
- IdeaA regulatory endpoint for drugs that block spread, not tumours
Shares Metastasis is understood least and studied last, Prostate cancer, HR-positive / HER2-negative breast cancer.