Techniques: Human induced pluripotent stem (iPS) cell-derived models of gliomagenesis for drug screening

Genetically engineered human iPS cell-derived models of gliomagenesis could be used to screen therapies for brain cancer. The cell models were generated from two sets of human iPS cells by a three-step process. First, mutant Src, mutant epidermal growth factor receptor (EGFR) and mutant Ras were expressed in the cells. Second, p53 was knocked down in one set of cells but left intact in the other. Third, both sets of cells were differentiated into neural progenitor cells. In both models, gene expression patterns were comparable to those of primary human glioma tumor-initiating cells. In a screen of 101 approved cancer drugs, Arranon nelarabine, Femara letrozole and the generic thymidylate synthetase (TYMS) inhibitor capecitabine decreased cell viability in both models and in primary glioma tumor-infiltrating cells with comparable potencies. Next steps could include using the models to screen compound libraries for novel glioma therapies.

Novartis AG markets Arranon, a DNA synthesis inhibitor, to treat acute lymphoblastic leukemia (ALL) and lymphoma...