7/ Unexpected: Phenformin also triggered changes in cholesterol pathways. This raises questions and maybe possibilities(?) for future drug combination strategies (e.g., phenformin + statins) to overcome resistance to mitochondrial inhibition. #CancerMetabolism

6/ Phenformin has risks in humans, including lactic acidosis, so is unlikely to be used clinically. But our findings pave the way for exploring safer mitochondrial-targeting drugs or combination therapies that target potential resistance pathways.

5/ We used phenformin, an older diabetes drug that was withdrawn from the market, to block mitochondrial OXPHOS in tumor cells and mouse models of DIPG.
We showed that in tumor spheroids hypoxia decreased.
In both cells and mouse models, radiosensitivity increased

3/ Hypoxia can make tumours more aggressive and resistant to radiation. Using clinical datasets, we identified hypoxia signatures in DIPG/DMG patient tumours and in DIPG mouse models. Tumours with ⬆️ hypoxia scores also had ⬆️ OXPHOS gene expression.

2/ We found patient-derived DIPG cell lines rely heavily on mitochondria for energy production via oxidative phosphorylation (OXPHOS). This consumes oxygen, potentially creating hypoxia. ⬇️#BrainTumor

📝 Paper alert: Targeting #DIPG tumor #metabolism, #mitochondria and #hypoxia to #radiosensitize tumors 🧠 ☢️ url.au.m.mimecastprotect.com/s/sijcCmO5gl...
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