Brain Tumor Organoids Key in Treating Glioblastomas

The findings of a new study published in the journal Cell suggest that glioblastoma organoids could serve as effective models to rapidly test personalized treatment strategies.

“While we’ve made important strides in glioblastoma research, preclinical and clinical challenges persist, keeping us from getting closer to more effective treatments,” said senior author Hongjun Song, PhD, Perelman Professor of Neuroscience in the Perelman School of Medicine at the University of Pennsylvania in a press release about the study. “One hurdle is the ability to recapitulate the tumor to not only better understand its complex characteristics, but also to determine what therapies post-surgery can fight it in a timelier manner.”

To conduct this study, the researchers extracted fresh tumor specimens from 52 patients to “grow” corresponding tumor organoids in the lab. The results showed that the overall success rate for generating glioblastoma organoids (GBOs) was 91%, with almost 67% percent of tumors expressing the IDH1 mutation, and 75 percent for recurrent tumors, within two weeks. These tumor glioblastoma organoids can also be biobanked and recovered later for analyses.

Moreover, the researchers conducted a molecular analyses in 12 patients to establish that these new GBOs had largely retained features from the primary tumor in the patient. Subsequently the researchers transplanted eight GBO samples into adult mouse models, which displayed rapid and aggressive detection of cancer cells while maintaining key mutation expression up to three months later. Importantly, a major hallmark of GBM — the infiltration of tumor cells into the surrounding brain tissue — was observed in the mouse models.

“These results highlight the potential for testing and treating glioblastomas with a personalized approach. The ultimate goal is to work towards a future where we can study a patient’s organoid and test which CAR T cell is going to be the best against their tumor, in real time.” O’Rourke said. “A shorter-term goal, given the heterogeneity of glioblastomas, is that in vitro testing of various therapeutic options may also help refine patient enrollment in clinical trials, by more accurately defining mutations and selecting the appropriate, available targeted therapies for each.”