Skip to content
BACK to News

Glioblastoma Models Get Boost From Cutting-Edge Tech

Published on February 19, 2020 in Research, Our Impact

Laboratory models are the backbone of cancer research and the development of new medicines. Researchers use models to study the biology of tumors like glioblastoma (GBM), as well as for testing the potential safety and effectiveness of drugs in different tumor types. 

Dr. Frank Furnari

While today’s models for glioblastoma research are the best tools scientists have to study the disease and potential new treatments, they still have a number of limitations.

Model development has been part of the focus of researchers in the National Brain Tumor Society’s Defeat GBM Research Collaborative. As recorded in the latest progress report from this program, the Defeat GBM team has already collaborated on the creation of more than 70 new model systems that mimic human GBM tumors with improved accuracy. These models have been deployed across the Defeat GBM teams to identify and validate a host of novel disease targets that new treatments could attack, as well as enabled testing of large libraries of compounds/drugs against these targets.

Now, using cutting-edge scientific technology (including stem cells and CRISPR gene-editing technology), a Defeat GBM-funded team from the University of California, San Diego, and Ludwig Cancer Research’s San Diego branch, led by Dr. Frank Furnari, has developed a new model system that could be the closest replica of human GBM tumors generated to date. 

We have developed stem cell models that are CRISPR-engineered to have tumor-associated driver mutations in glioblastoma, which harbor essentially all features of patient-derived tumors, including extrachromosomal DNA applications. These models, or avatars as we call them, enable us to study human tumor development over long periods in vivo, which has not been feasible with patient-derived tissue samples, which already harbor other genetic changes.

Attribution: Dr. Furnari

Specifically, Dr. Furnari and his colleagues, including his Defeat GBM collaborator, Dr. Paul Mischel, used the CRISPR gene-editing technology to “make precise mutations” in the “otherwise ‘normal’ genome” of isolated stem cells, which were then engrafted into lab mice. The implanted cells ultimately induced the formation of tumors that look and behave remarkably similar to human glioblastoma. Analysis of these models with advanced “single-cell” tumor sequencing technology confirmed the avatars have a similar mosaic of mutations and other genomic and molecular alterations as seen in tumor biopsy samples taken from patients.

This avatar mimics the intra-tumor heterogeneity observed in people, making it a good option for detailed examination of tumor evolution and searching for therapeutic vulnerabilities. 

Attribution: Dr. Furnari

Ultimately, the innovation of Dr. Furnari and his colleagues will accelerate the evaluation of potential drugs while increasing the likelihood of successful translation of research from the lab to the clinic.

These avatars were described in the January 20, 2020 issue of the leading scientific journal Nature Communications.

Stay Informed & Connected