One big problem in treating cancer is that the same medicine works well for some people but not for others. Researchers at the MRC Laboratory of Medical Sciences studied why this happens with a group of drugs called PARP inhibitors.
They looked at tiny pieces of ovarian tumors taken from patients and kept them alive in the lab. By adding the drugs to these pieces, the scientists could watch how the medicines moved inside real human tissue.
How the Drugs Spread Inside Tumors
Using special imaging tools, the team made maps that show where the drugs gathered inside the tumor. They also checked which genes were active in areas with lots of drug and in areas with little drug.
They found big differences. Even when the same dose was used, some parts of a tumor had a lot of medicine while other parts had very little.
Lysosomes Hold the Drugs
The reason for this uneven spread is that tiny compartments inside cells, called lysosomes, can trap the drugs. Think of lysosomes as small storage rooms. Some PARP inhibitors get stuck there and are released slowly, creating pockets of high drug concentration.
Not all PARP inhibitors act the same way. Drugs such as rucaparib and niraparib are stored in lysosomes, while olaparib mostly avoids them.
What This Means for Patients
PARP inhibitors are already used to treat ovarian, breast, and prostate cancers. Understanding how these medicines are stored inside cells could help doctors choose the right drug for each patient, making treatment more effective and reducing the chance of resistance.
In real patients, the medicines travel through the bloodstream and must pass through irregular tumor blood vessels. This can add more unevenness to drug delivery. Future research will use animal models and larger groups of patients to see how blood flow, tumor structure, and lysosome storage work together.
This work was funded by the Medical Research Council, Cancer Research UK, and several other partners.