Among all cancers, glioblastoma (GBM) remains one of the least treatable. One key factor in this resistance is a subpopulation of tumor cells termed glioma stem cells (GSCs). These cells are highly resistant to current treatment modalities, possess marked self-renewal capacity, and are considered key drivers of tumor recurrence. Further complicating an understanding of GBM, evidence shows that the GSC population is not a pre-ordained and static group of cells but also includes previously differentiated GBM cells that have attained a GSC state secondary to environmental cues. The metabolic behavior of GBM cells undergoing plasticity remains incompletely understood. To that end, we probed the connection between GSCs, environmental cues, and metabolism. Using patient-derived xenograft cells, mouse models, transcriptomics, and metabolic analyses, we found that cell state changes are accompanied by sharp changes in metabolic phenotype. Further, treatment with temozolomide, the current standard of care drug for GBM, altered the metabolism of GBM cells and increased fatty acid uptake both in vitro and in vivo in the plasticity driven GSC population. These results indicate that temozolomide-induced changes in cell state are accompanied by metabolic shifts—a potentially novel target for enhancing the effectiveness of current treatment modalities.

A man in his late 60s with prior Hartman’s procedure underwent colostomy takedown and complex ventral hernia repair. He subsequently developed gastrointestinal (GI) bleeding from a duodenal bulb ulcer. Despite five endoscopic procedures aimed at achieving haemostasis, including placement of an over-the-scope clip, and four endovascular embolisations (inferior and superior pancreaticoduodenal, right gastroepiploic and gastroduodenal arteries), the patient continued to experience episodic, haemodynamically significant bleeding. He eventually required emergency exploratory laparotomy, where the proper hepatic artery was identified as the source (a previously unreported phenomenon). He underwent antrectomy and proper hepatic artery ligation. This case highlights the need to interrogate all portions of the hepatic vasculature in the treatment of refractory GI bleeding.