{"entity":{"id":"idea-metabolic-vulnerability-mapping","kind":"idea","name":"Map metabolic dependencies in the patient, not the dish","aka":[],"tldr":"Metabolic drugs keep failing because tumours switch fuels. Measuring what a patient's tumour actually eats, with tracers and PET, could pick the right metabolic drug for the right tumour.","summary":"This idea proposes mapping metabolic dependencies in the patient rather than the dish: tumours switch fuels, so measuring what a tumour consumes with PET tracers could match drug to tumour. Isotope tracing in patients (DeBerardinis) shows in vivo fuel use differs from culture, FDG, glutamine (18F-FGln) and acetate tracers exist, and glutaminase inhibitors failed in unselected populations. The hypothesis is that tracer-defined phenotypes (glycolytic, glutamine- or lipid-dependent) predict response to matched inhibitors, because imaging reads tumour metabolism non-invasively. The test is a basket trial assigning therapy by baseline 18F-FGln and FDG PET in Non-small-cell lung cancer, Renal cell carcinoma and Glioma & glioblastoma (Cancer metabolism pathway).","asOf":"2026-09-08","links":[{"label":"Faubert et al., Lactate metabolism in human lung tumours (Cell 2017)","url":"https://doi.org/10.1016/j.cell.2017.09.019"}],"tags":["mechanism","open-question"],"related":[],"cancers":["nsclc","rcc","glioblastoma"],"sections":[],"technologies":["fdg-pet","pet"],"targets":[],"drugs":[],"companies":[],"institutions":["mskcc","md-anderson"],"pathways":["cancer-metabolism","keap1-nrf2"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-faubert-cell"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Tracer-defined metabolic phenotypes (glycolytic, glutamine-dependent, lipid-dependent) predict response to matched metabolic inhibitors, rescuing agents that failed in unselected trials.","rationale":"Tumour metabolism is heterogeneous and plastic; imaging can read it non-invasively and repeatedly.","test":"Basket trial with baseline 18F-FGln and FDG PET assigning glutaminase inhibitor or glycolysis-targeting agent, with PET flux change at 2 weeks as pharmacodynamic endpoint.","maturity":"preclinical-evidence"},"route":"/ideas/idea-metabolic-vulnerability-mapping/","neighbours":{"cancer":[{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"technology":[{"id":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"},{"id":"pet","kind":"technology","name":"PET (positron emission tomography)","route":"/technologies/pet/"}],"institution":[{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","route":"/institutions/md-anderson/"},{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"}],"pathway":[{"id":"cancer-metabolism","kind":"pathway","name":"Cancer metabolism","route":"/pathways/cancer-metabolism/"},{"id":"keap1-nrf2","kind":"pathway","name":"KEAP1-NRF2 antioxidant pathway","route":"/pathways/keap1-nrf2/"}],"paper":[{"id":"paper-faubert-cell","kind":"paper","name":"Lactate Metabolism in Human Lung Tumors","route":"/key-papers/paper-faubert-cell/"}]}}