For many cancer patients, it is not clear at the outset which treatment will have the highest chance for success. Many cancer treatments have significant side effects, which can occur whether the drug provides any benefit to the patient or not. If it is possible to know at the outset the likelihood of treatment success for the various available drugs, the patient and doctor can choose a treatment course with the highest chance for success while minimizing the side effects and costs of ineffective treatments. Sometimes patients can be stratified on the basis of a marker from a biopsy of their cancer, but often they cannot, and it is not clear which treatments should be undertaken. Therefore, the process of finding the right drug is often trial and error.
Ideally, a patient's cells could be tested ex vivo against the possible drugs to see which is most effective. When the patient's cells are initially removed and tested, the cells may be sick or dying and results of drug screening at this point could be misleading. The authors* describe a method of expanding and stabilizing the human patient's cancer cells in a modified mouse (hypoxanthine phosphoribosyl transferase [hprt]–null immunodeficient mouse) and then removing those cells and testing the cells for drug sensitivity in an in vitro cell assay (see Figure 1).
One of the important aspects of their research was that their modified mouse allows the noncancer fibroblasts of the human patient to be replaced by biochemically defective mouse cells, which can be selectively eliminated prior to the cell assay (by means of hypoxanthine, aminopterin, and thymidine [HAT]–containing media). In culture, the noncancer fibroblasts can overtake the cancer cells, so this method of stromal cell removal allows for the malignant cancer cells to be retained. This method was successful in seven of the nine cell lines attempted (six pancreatic ductal adenocarcinoma cell lines and one ovarian cancer cell line). One of the pancreatic lines (Panc502) was isolated from the mouse and used to test the in vitro sensitivity to a drug panel containing over 3,000 drugs (Johns Hopkins drug library panel, see Figure 2).