Metabolic therapy: starving the tumour of a nutrient
Removing an amino acid or nutrient that certain tumours cannot make for themselves, while normal cells can.
Arginine deprivation with pegargiminase (ADI-PEG 20) exploits ASS1 loss; the phase 2/3 ATOMIC-Meso study in mesothelioma completed (NCT02709512), while the phase 3 leiomyosarcoma study (NCT05712694) and a lung study were terminated. Glutaminase inhibition failed in renal cancer, asparaginase remains standard in ALL, and dietary approaches such as ketogenic or fasting-mimicking regimens have only small randomised trials with mixed results. The lesson so far is that metabolic dependencies are real but narrow.
How it works
Enzymatic depletion of a circulating nutrient (arginine, asparagine, methionine) kills tumour cells that have lost the biosynthetic enzyme, while normal cells resynthesise it.
- Genotype-defined patient selection, for example ASS1 loss
- Precedent: asparaginase cures a share of ALL
- Combines with chemotherapy
- Repeated failures outside narrow settings
- Antibody responses to pegylated enzymes
- Diet-based approaches lack rigorous evidence
Latest papers
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