Find the parts of a tumour the drug never reaches
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.
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.
- Acquired resistance to every therapy · Nearly every targeted therapy stops working within months to a few years as the tumour adapts.
- Tumour heterogeneity and clonal evolution · A tumour is many tumours. Treatments that kill most cells leave the rest to grow back, changed.
- Wrong doses · Most drug doses were chosen as the highest a person can tolerate, which is often more than they need.
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