It won in culture. It lost in tissue.
A tumor is not one environment. Oxygen, acidity and pressure shift over distances shorter than a hundred micrometers, and each shift changes what your compound does. An average describes nowhere inside the mass.
The problem
Some regions are well perfused and some are barely reached. Oxygen falls away from vessels, acidity follows, pressure rises where drainage is poor. Hypoxia changes which death pathways exist at all. Acidity changes whether a molecule crosses a membrane. Across one mass, one compound is not one compound. Reported as one average, a tumor looks mildly hypoxic, mildly acidic and mildly pressurized. No region in it is that object.
What comes back
- The fraction of the mass where the compound works, and the fraction where it cannot
- What would have to change to move the split
- Why the culture winner underperformed in tissue
- Which conditions a program should be screening against in the first place
The decision it changes
The average lets a team believe a compound half-works everywhere. Usually it works well in one region and not at all in another. Same number, two different programs. A team that can see the split decides which region to fix. A team holding the average spends another year arguing about whether the compound works at all.