# Metabolic therapy: starving the tumour of a nutrient

Source: https://onco.cc/technologies/metabolic-therapy/  
OnCo record `metabolic-therapy` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Removing an amino acid or nutrient that certain tumours cannot make for themselves, while normal cells can.

## Summary

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.

## Fields

- Kind: Technology
- Status: phase-2
- Last checked: 2026-09-08
- Tags: frontier
- Principle: Enzymatic depletion of a circulating nutrient (arginine, asparagine, methionine) kills tumour cells that have lost the biosynthetic enzyme, while normal cells resynthesise it.
- Strengths: Genotype-defined patient selection, for example ASS1 loss; Precedent: asparaginase cures a share of ALL; Combines with chemotherapy
- Limitations: Repeated failures outside narrow settings; Antibody responses to pegylated enzymes; Diet-based approaches lack rigorous evidence

## Sources

- ATOMIC-Meso phase 2/3 (NCT02709512): https://clinicaltrials.gov/study/NCT02709512
- ARGSARC phase 3, terminated (NCT05712694): https://clinicaltrials.gov/study/NCT05712694

## Connected records

- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/), [Mesothelioma](https://onco.cc/cancers/mesothelioma/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)
- fronts: [Chemotherapy](https://onco.cc/fronts/chemotherapy/), [Diet, Exercise & Lifestyle](https://onco.cc/fronts/nutrition-lifestyle/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Exercise & lifestyle oncology](https://onco.cc/technologies/exercise-oncology/), [Fasting and fasting-mimicking diets around chemotherapy](https://onco.cc/technologies/fasting-mimicking-diet/), [Ketogenic diets in glioblastoma](https://onco.cc/technologies/ketogenic-diet-glioblastoma/), [Synthetic lethality approaches](https://onco.cc/technologies/synthetic-lethality-approaches/)
- pathways: [Glutamine addiction](https://onco.cc/pathways/glutamine-metabolism/), [Lipid synthesis, uptake & cholesterol](https://onco.cc/pathways/lipid-metabolism-cancer/), [Nutrient competition & metabolic immunosuppression](https://onco.cc/pathways/nutrient-competition-tme/)
- roadmaps: [Radical oncology: what could change the war by 2035](https://onco.cc/roadmaps/frontier-2035/)
- terms: [Metabolic theory of cancer: from Warburg to oncometabolites](https://onco.cc/terms/metabolic-theory-of-cancer/), [Warburg-effect diet claims ('sugar feeds cancer')](https://onco.cc/terms/warburg-effect-diet-claims/)
- trials: [ERGO2: ketogenic diet and fasting during re-irradiation of recurrent glioma](https://onco.cc/trials/ergo2/)
- ideas: [One definitive ketogenic diet trial in glioblastoma, then stop](https://onco.cc/ideas/idea-nl-ketogenic-gbm-definitive-trial/)
- institutions: [Harold C. Simmons Comprehensive Cancer Center, UT Southwestern](https://onco.cc/institutions/utsw-simmons/), [Holden Comprehensive Cancer Center, University of Iowa](https://onco.cc/institutions/iowa-holden/), [Rosalind and Morris Goodman Cancer Institute, McGill University](https://onco.cc/institutions/mcgill-goodman/), [Rutgers Cancer Institute of New Jersey](https://onco.cc/institutions/rutgers-cinj/), [Salk Institute Cancer Center](https://onco.cc/institutions/salk-institute/)

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