Significance:
Glioblastoma (GBM), the most common and lethal
primary brain tumor with a median survival rate of only 15 months and a 5-year survival rate of only 6.8%, remains largely incurable despite the intensive
multimodal treatment of surgical resection and
radiochemotherapy. Developing effective new
therapies is an unmet need for patients with GBM. Recent Advances: Targeted
therapies, such as antiangiogenesis
therapy and
immunotherapy, show great promise in treating GBM based upon increasing knowledge about
brain tumor biology. Single-cell transcriptomics reveals the plasticity, heterogeneity, and dynamics of
tumor cells during GBM development and progression. Critical Issues: While antiangiogenesis
therapy and
immunotherapy have been highly effective in some types of
cancer, the disappointing results from clinical trials represent continued challenges in applying these treatments to GBM. Molecular and cellular heterogeneity of GBM is developed temporally and spatially, which profoundly contributes to therapeutic resistance and
tumor recurrence. Future Directions: Deciphering mechanisms of
tumor heterogeneity and mapping
tumor niche trajectories and functions will provide a foundation for the development of more effective
therapies for GBM patients. In this review, we discuss five different
tumor niches and the intercellular and intracellular communications among these niches, including the perivascular, hypoxic, invasive, immunosuppressive, and
glioma-stem cell niches. We also highlight the cellular and molecular biology of these niches and discuss potential strategies to target these
tumor niches for GBM
therapy. Antioxid. Redox Signal. 39, 904-922.