CRISPR replicas

The trouble with many models of cancer is that they do not authentically replicate the cellular and microenvironmental complexity of tumors that arise spontaneously and evolve over time in animals. In a January Nature Communications paper, Ludwig San Diego’s Frank Furnari and colleagues describe their construction and evaluation of a new genetically engineered model for the brain cancer glioblastoma (GBM) that addresses this limitation. The model is developed from human induced pluripotent stem cells (iPSC)—which can give rise to a number of tissues—engineered using CRISPR (a method for directed gene editing) to replicate known genetic drivers of GBM. When engrafted into the brains of mice, the engineered iPSCs gave rise to authentic GBM tumors that, when re-engrafted into other mice, faithfully replicated the cellular heterogeneity and other common traits of patient-derived tumors. The models also enabled the tracing of the tumor’s evolution and development of drug resistance. Frank and his colleagues plan to use their model to screen drugs and test other mutations in adult and pediatric brain tumors. They’re also using their approach to model tumors in other tissues, such as the pancreas and lung.

This article appeared in the August 2020 issue of Ludwig Link. Click here to download a PDF (2 MB).


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