New approaches to model glioblastoma in vitro using brain organoids: implications for precision oncology

Abstract

Glioblastoma is an aggressive form of primary brain cancer for which new treatment approaches are desperately needed. To achieve this goal, better experimental approaches to study human glioblastoma are required; and in particular, methods that recapitulate the native tumor microenvironment will be most valuable. In accordance with this need, Howard Fine and co-workers have developed a new experimental model, termed GLICO (1), which should facilitate a better understanding of the biology of the disease, and importantly, enable more reliable testing of potential new therapies. Currently, standard therapy for glioblastoma involves surgery to achieve maximal safe resection, combined with radiotherapy and temozolomide chemotherapy. However, despite this multi-modal approach, tumor recurrence is almost inevitable, after which no treatments that effectively prolong survival exist (2,3). Median survival time from diagnosis is only 15 months, and the 5-year relative survival (just 4.6% at 5 years) has remained stable over the last three decades. Considering this dismal situation, there is intense interest in developing new treatments for glioblastoma. So far, however, those treatments that appeared initially effective against cultured cell lines and mouse tumor models have generally failed in the clinic (4). Possibly, more sophisticated experimental systems, such as that developed by Linkous et al. (1), will allow for more accurate prediction of the therapeutic efficacy of potential new treatments. And because this system mimics the native glioblastoma microenvironment, it may also facilitate the development of novel agents that specifically target non-malignant aspects of the tumor microenvironment, especially the extracellular matrix (ECM) and the neuronal and glial compartments.