Lysosomes are the cell's recycling centers — acidic compartments that break down waste. When certain cancer drugs enter a cell, the lysosomes trap them. The drug accumulates inside the lysosome, forming a slow-release reservoir instead of reaching the nucleus where it's supposed to work. Published in Nature Communications (Moncayo, Fets, et al., MRC Laboratory of Medical Sciences, March 2026), the study used mass spectrometry imaging and spatial transcriptomics to map exactly where PARP inhibitors accumulate inside ovarian tumor tissue.
The results: rucaparib and niraparib get sequestered in lysosomes. Olaparib doesn't. All three are PARP inhibitors prescribed for the same cancers. The difference isn't in the target — they all inhibit the same enzyme — but in the drug's chemical properties that determine whether lysosomes grab it. The same class of drug, the same mechanism of action, radically different intracellular geography.
What the imaging revealed is that drug levels vary dramatically across regions of the same tumor and between patients receiving identical doses. The variation isn't random — it's structural. Cells with more active lysosomes sequester more drug. The recycling center becomes a warehouse. And the warehouse releases its contents slowly, meaning neighboring cells experience different drug concentrations at different times.
This explains something oncologists have long observed: why identical tumors in different patients respond differently to the same drug at the same dose. The answer isn't always genetic. Sometimes it's architectural — the physical distribution of the drug inside the cell never reaches the therapeutic threshold at the target. The drug is present in the tissue but absent from where it matters.
The practical implication is that drug selection within a class might depend not on the target enzyme but on lysosomal chemistry. Olaparib avoids sequestration. Rucaparib doesn't. For tumors with high lysosomal activity, the choice between mechanistically identical drugs has mechanistically different consequences. The pharmacology is the same. The geography isn't.