I left off last time saying that we have two big issues to address with regard to hypoxia as a cause or exacerbating factor in cancer:
- What causes tissue to become hypoxic?
- Is there a role for hyperbaric oxygen therapy in fighting cancer?
Let’s tackle them in order.
To be honest with you, I still don’t know which comes first: low oxygen, or mitochondrial dysfunction. The fact is, even when there’s plenty of oxygen available, if the mitochondria are malfunctioning, they can’t use it. But what if what’s causing the mitochondria to malfunction is insufficient oxygen? (I told you last time this stuff is complicated!)
It almost doesn’t matter, right? The bottom line is, whether the tissue is hypoxic or not, the mitochondria are not using whatever oxygen might be present. (Well, they’re using some of it. Remember, kids, when it comes to biology and biochemistry, there are very rarely any absolutes, yes or no, on or off. Things aren't binary, but rather, there's a balancing act. Even cancer cells have some mitochondria that are okay; it’s just that the majority of them are messed up.)
I just have a hard time wrapping my head around it all. Think about angiogenesis: the creation of blood vessels specifically so that the cancerous tissue ensures it has a steady supply of fuel and nutrients. But what does blood carry besides fuel and nutrients? OXYGEN. So you would think that angiogenesis would give cancer cells more oxygen, not less. So going one step further, this being the case, it seems like the mitochondrial dysfunction comes first, because theoretically, there should be sufficient oxygen delivery to the cancer cells, what with all those blood vessels they created for their own nefarious purposes. So there is sufficient oxygen (“normoxia”), yet we have hypoxia-inducible factors out the yin-yang upregulating all sorts of nasty pathways and reactions in these cells to keep themselves alive because they think they’re hypoxic. And the reason they think they’re hypoxic is because the mitochondria aren’t using the oxygen. (That’s my logic, anyway. I told you there was going to be a lot of wild speculation here, and so it begins.)