Patient-derived experimental models are developed by using a small piece of the patient’s tumor, which can be implanted under the skin or in an organ of a mouse (patient-derived xenograft), or cultured in a dish (patient-derived cell model). Additionally, blood cells from the same patient can be grown in a dish to represent normal cells. These laboratory techniques aim to closely mimic how the patient’s cells behave in the human body, providing valuable insights for research and treatment development.

Once tumor cells are growing in the lab, we can:

–Study how the disease develops: Scientists look at genes and proteins in the growing tumor cells and compare what they see to the normal cells from the blood to find what is unique to the tumor. This is sometimes referred to as identifying tumor “drivers”.

–Test new potential therapies: Researchers can add new potential chemotherapies (chemical compounds) to the growing cells in a dish to identify which compounds can kill the tumor cells, but not kill the normal cells. Then, they can treat mice that bear growing tumor xenografts with these new potential treatments, or use new combinations of known drugs, to see if they are effective at shrinking the tumor growing in the mouse, in the same way they would treat a human patient. This step is unfortunately necessary because not all drugs that can kill tumor cells in a dish are effective at killing the cells of a tumor growing in a living organism. They also need to evaluate the dosage needed because some drugs can have toxic effects on the living organism at the dose required, which scientists need to identify before using the drug on human patients.

–Study drug resistance: Sometimes tumor cells start growing again after treatment (recurrence) or stop responding to treatment during therapy. Here researchers will look again at genes and proteins to see what changed in the growing tumor cells that continue to grow after being exposed to the treatment. They will use that information to modify the treatment strategy and overcome treatment resistance (e.g. test different doses of drugs, or different combinations used together).

Usually, the next step after research using model systems is to run human clinical trials to test the effectiveness of the new proposed treatment. But when dealing with a rare cancer, there are not enough patients to run conventional trials that require statistical analyses and a placebo group. So, the next best option is to use the information gained from one patient’s tumor in “mouse trials” to guide better treatment for the next patient with a similar disease, which is why it is so important for every patient who can participates in research to do so.