Research into therapeutic targets for glioma has identified critical molecular dependencies that could lead to novel treatment strategies. One significant study utilized CRISPR/Cas9 loss-of-function gene deletion screens to uncover PIK3CA and MTOR as targetable genetic dependencies in diffuse intrinsic pontine glioma (DIPG) models. The findings suggest that the PI3K/Akt/mTOR inhibitor, paxalisib, could be a promising therapeutic option, as mice treated with this inhibitor exhibited systemic glucose feedback and increased insulin levels, paralleling patient responses to PI3K inhibitors (ref: Duchatel doi.org/10.1172/JCI170329/). This highlights the potential for targeted therapies that can penetrate the blood-brain barrier and address the aggressive nature of these tumors. Additionally, the study emphasizes the need for further exploration into the efficacy of such inhibitors in clinical settings, given the uniformly fatal prognosis associated with DIPG. Another important aspect of glioma research is the role of nicotinic acetylcholine receptors (nAChRs) in tumor proliferation. A study analyzing GBM transcriptomes revealed spatial heterogeneity in nAChR subtype expression, particularly focusing on the α1*, α7, and α9 subtypes. The use of subtype-selective neurotoxic inhibitors demonstrated that these receptors can enhance the proliferation of patient-derived glioblastoma cell lines, suggesting that targeting specific nAChR subtypes could provide a therapeutic avenue. However, the study also cautioned that the presence of fetal bovine serum in culture media could alter nAChR expression and functioning, which may impact the reliability of these models (ref: Gondarenko doi.org/10.3390/toxins16020080/). This underscores the complexity of glioma biology and the necessity for precise methodologies in therapeutic development.