{"entity":{"id":"metabolic-therapy","kind":"technology","name":"Metabolic therapy: starving the tumour of a nutrient","aka":[],"tldr":"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.","status":"phase-2","asOf":"2026-09-08","links":[{"label":"ATOMIC-Meso phase 2/3 (NCT02709512)","url":"https://clinicaltrials.gov/study/NCT02709512"},{"label":"ARGSARC phase 3, terminated (NCT05712694)","url":"https://clinicaltrials.gov/study/NCT05712694"}],"tags":["frontier"],"related":[],"cancers":["mesothelioma","all-leukemia","sarcoma"],"sections":["targeted-therapy","chemotherapy","nutrition-lifestyle"],"technologies":["cytotoxic-chemotherapy","synthetic-lethality-approaches","exercise-oncology"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["lipid-metabolism-cancer"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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"]},"route":"/technologies/metabolic-therapy/","neighbours":{"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"},{"id":"mesothelioma","kind":"cancer","name":"Mesothelioma","route":"/cancers/mesothelioma/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"section":[{"id":"chemotherapy","kind":"section","name":"Chemotherapy","route":"/fronts/chemotherapy/"},{"id":"nutrition-lifestyle","kind":"section","name":"Diet, Exercise & Lifestyle","route":"/fronts/nutrition-lifestyle/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"exercise-oncology","kind":"technology","name":"Exercise & lifestyle oncology","route":"/technologies/exercise-oncology/"},{"id":"fasting-mimicking-diet","kind":"technology","name":"Fasting and fasting-mimicking diets around chemotherapy","route":"/technologies/fasting-mimicking-diet/"},{"id":"ketogenic-diet-glioblastoma","kind":"technology","name":"Ketogenic diets in glioblastoma","route":"/technologies/ketogenic-diet-glioblastoma/"},{"id":"synthetic-lethality-approaches","kind":"technology","name":"Synthetic lethality approaches","route":"/technologies/synthetic-lethality-approaches/"}],"pathway":[{"id":"glutamine-metabolism","kind":"pathway","name":"Glutamine addiction","route":"/pathways/glutamine-metabolism/"},{"id":"lipid-metabolism-cancer","kind":"pathway","name":"Lipid synthesis, uptake & cholesterol","route":"/pathways/lipid-metabolism-cancer/"},{"id":"nutrient-competition-tme","kind":"pathway","name":"Nutrient competition & metabolic immunosuppression","route":"/pathways/nutrient-competition-tme/"}],"roadmap":[{"id":"frontier-2035","kind":"roadmap","name":"Radical oncology: what could change the war by 2035","route":"/roadmaps/frontier-2035/"}],"term":[{"id":"metabolic-theory-of-cancer","kind":"term","name":"Metabolic theory of cancer: from Warburg to oncometabolites","route":"/terms/metabolic-theory-of-cancer/"},{"id":"warburg-effect-diet-claims","kind":"term","name":"Warburg-effect diet claims ('sugar feeds cancer')","route":"/terms/warburg-effect-diet-claims/"}],"trial":[{"id":"ergo2","kind":"trial","name":"ERGO2: ketogenic diet and fasting during re-irradiation of recurrent glioma","route":"/trials/ergo2/"}],"idea":[{"id":"idea-nl-ketogenic-gbm-definitive-trial","kind":"idea","name":"One definitive ketogenic diet trial in glioblastoma, then stop","route":"/ideas/idea-nl-ketogenic-gbm-definitive-trial/"}],"institution":[{"id":"utsw-simmons","kind":"institution","name":"Harold C. Simmons Comprehensive Cancer Center, UT Southwestern","route":"/institutions/utsw-simmons/"},{"id":"iowa-holden","kind":"institution","name":"Holden Comprehensive Cancer Center, University of Iowa","route":"/institutions/iowa-holden/"},{"id":"mcgill-goodman","kind":"institution","name":"Rosalind and Morris Goodman Cancer Institute, McGill University","route":"/institutions/mcgill-goodman/"},{"id":"rutgers-cinj","kind":"institution","name":"Rutgers Cancer Institute of New Jersey","route":"/institutions/rutgers-cinj/"},{"id":"salk-institute","kind":"institution","name":"Salk Institute Cancer Center","route":"/institutions/salk-institute/"}]}}