Starve the survivors: target the energy pathway drug-tolerant cells switch to
Cells that survive treatment often change how they make energy, relying on burning fat rather than sugar. Blocking that switch might finish them off.
Drug-tolerant persisters and residual disease cells show increased oxidative phosphorylation and fatty acid oxidation dependence in melanoma, lung and leukaemia models. OXPHOS and fatty acid oxidation inhibitors have entered early clinical testing, with tolerability as the main issue. The proposal is intermittent, response-triggered administration at the point of maximal response rather than continuous use in bulk disease.
- Acquired resistance to every therapy · Nearly every targeted therapy stops working within months to a few years as the tumour adapts.
- 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.
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