# Map metabolic dependencies in the patient, not the dish

Source: https://onco.cc/ideas/idea-metabolic-vulnerability-mapping/  
OnCo record `idea-metabolic-vulnerability-mapping` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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).

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Tags: mechanism; open-question
- 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.
- Proposed 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

## Sources

- Faubert et al., Lactate metabolism in human lung tumours (Cell 2017): https://doi.org/10.1016/j.cell.2017.09.019

## Connected records

- cancers: [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/)
- technologies: [FDG PET](https://onco.cc/technologies/fdg-pet/), [PET (positron emission tomography)](https://onco.cc/technologies/pet/)
- institutions: [MD Anderson Cancer Center](https://onco.cc/institutions/md-anderson/), [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- pathways: [Cancer metabolism](https://onco.cc/pathways/cancer-metabolism/), [KEAP1-NRF2 antioxidant pathway](https://onco.cc/pathways/keap1-nrf2/)
- key papers: [Lactate Metabolism in Human Lung Tumors](https://onco.cc/key-papers/paper-faubert-cell/)

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