October, 2021 Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient-Derived Xenografts and Direct-from-Patient Screening

Cancer Discovery 

One way to discover new drug treatments for a disease of interest is to test drugs that have already been shown to work for other conditions. Because such repurposed drugs have already been widely tested, some steps in getting them approved can be accelerated. The chance that any one drug will prove useful is small, but if many can be tested the chances of success grow. To test many drugs requires a method that gives quick, efficient, affordable and relevant results. 

In the work described here, drug testing was done using cells taken from tumors of FLC patients that were then transplanted in mice. The group showed that these tumors in mice retained all of the properties of the tumors found in patients.  Human cells taken from the mouse-passaged tumors can be dispensed by automated equipment into plastic plates, each with thousands of wells. Each well contains a small volume of a solution that keeps the cells alive for a time. To each well a drug is added, and the cells subsequently monitored for viability. Because the volume of each well is small, not much of each drug is consumed. Used robotic manipulation and cell monitoring, thousands of drugs were tested. Those of interest damaged FLC cells more than the comparison cells, those that resemble normal liver. Among the drugs identified were inhibitors of topoisomerase 1, inhibitors of histone deacetylase and napabucasin. The results were confirmed by testing FLC cells freshly removed by surgery from patients. Testing direct-from-patient cells could in the future help in promptly choosing the best drug for the individual patient.

Written by Dr. Phil Coffino