# Find the parts of a tumour the drug never reaches

Source: https://onco.cc/ideas/idea-bio1-drug-exposure-sanctuary-mapping/  
OnCo record `idea-bio1-drug-exposure-sanctuary-mapping` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Cells that receive only a small amount of a drug survive and adapt. Measuring where inside a tumour the drug actually reaches would show where resistance is being bred.

## Summary

Sub-therapeutic exposure regions, created by poor perfusion, high interstitial pressure and dense stroma, are where selection for resistance is strongest. Imaging mass spectrometry on resected specimens, microdose PET with labelled analogues and intratumoural microdialysis can map drug concentration spatially. Linking these maps to regional clonal composition would show whether resistant clones arise preferentially in low-exposure zones.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Resistant subclones are enriched in tumour regions with the lowest measured drug concentration, establishing under-exposure rather than intrinsic biology as a major driver of resistance.
- Rationale: Antibiotic resistance evolves fastest in concentration gradients, an experimentally demonstrated principle; tumours plausibly create the same gradients but the measurement is rarely made.
- Proposed test: Neoadjuvant window study: dose before surgery, then perform imaging mass spectrometry and region-matched sequencing on the resected tumour to test the spatial association.
- Maturity: speculative
- Actor: research

## Sources

- Bottleneck evidence (Acquired resistance to every therapy): Soria et al., Osimertinib in untreated EGFR-mutated NSCLC (FLAURA, NEJM 2018): https://doi.org/10.1056/NEJMoa1713137

## Connected records

- technologies: [PET (positron emission tomography)](https://onco.cc/technologies/pet/), [Proteomics & phosphoproteomics](https://onco.cc/technologies/proteomics/), [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/)
- terms: [Drug resistance (primary and acquired)](https://onco.cc/terms/resistance/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/), [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)

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