I appreciate the effort to map out the oxidative stress landscape in breast cancer, especially the way this paper connects glucose metabolism to redox balance. But there’s something that doesn’t sit right in how glycolysis is framed as a targetable vulnerability.
The paper puts a lot of weight on the idea that inhibiting glycolysis could push cancer cells into oxidative stress and sensitize them to therapy. But this interpretation seems to gloss over a pretty well-established fact: breast cancer cells, especially aggressive types like TNBC, are metabolically flexible. We’ve known for a while that when glucose is limited, these cells don’t just shut down. They pivot. Glutaminolysis kicks in, serine metabolism ramps up, and mitochondrial pathways take over to keep NADPH and ATP production going. In other words, cutting off glycolysis alone might not induce the level of oxidative stress the paper implies, at least not reliably.
It’s also a bit inconsistent that the review acknowledges these other redox-supporting pathways but doesn’t address how they might compensate if glycolysis is targeted. That’s a big omission when you’re building a case for targeting oxidative stress therapeutically. If these alternate pathways are active, and we know they often are, then the argument for glycolytic inhibition as a standalone strategy starts to lose ground.
So, the key question is: how do the authors see this playing out in a real tumor context, where metabolic rewiring happens fast? Without a clearer picture of how compensatory mechanisms are accounted for, it feels like the therapeutic takeaway is oversimplified, and that could be misleading in how this gets translated into actual treatment approaches.