The role of autophagy in glioblastoma cell sensitivity to therapeutic agents has garnered significant attention, particularly in the context of Selinexor, a selective inhibitor of exportin-1 (XPO1). Selinexor's mechanism of action involves the induction of apoptosis, but recent findings suggest that autophagy also plays a critical role in modulating this sensitivity. In a study by Tang, it was demonstrated that genetic or pharmacologic suppression of autophagy significantly sensitized glioblastoma cells to Selinexor-induced toxicity, leading to enhanced apoptotic responses. This indicates that autophagy may serve as a protective mechanism for glioblastoma cells against the cytotoxic effects of Selinexor, highlighting the complexity of therapeutic responses in this aggressive cancer type (ref: Tang doi.org/10.1093/neuonc/). The interplay between autophagy and apoptosis in glioblastoma presents a potential avenue for therapeutic intervention, suggesting that targeting autophagy could enhance the efficacy of existing treatments. Further investigations are warranted to elucidate the precise molecular pathways involved and to explore the potential of combining autophagy inhibitors with Selinexor for improved treatment outcomes.

The transition of glioblastoma cells to a mesenchymal-like state is a critical factor in the aggressiveness and treatment resistance of this tumor type. Zhao's research highlights the role of HDAC7 in driving this transition through LGALS3-mediated interactions between cancer cells and macrophages. By integrating single-cell and spatial transcriptomic data, the study revealed that mesenchymal (MES) glioblastoma cells exhibit a tight localization with macrophage-derived microenvironments, suggesting a significant crosstalk that facilitates tumor progression. The upregulation of HDAC7, regulated by SUMOylation, was identified as a key factor in this process, indicating that epigenetic modifications play a crucial role in the mesenchymal transition of glioblastoma cells (ref: Zhao doi.org/10.7150/thno.100939/). This finding underscores the importance of the tumor microenvironment in influencing glioblastoma behavior and suggests that targeting the HDAC7-LGALS3 axis could provide new therapeutic strategies to combat the aggressive nature of MES glioblastoma. The interplay between tumor cells and immune components, such as macrophages, further complicates the treatment landscape, necessitating a multifaceted approach to glioblastoma therapy.