Is bigger better? Normally not in medicine. It is the evolutionary prerogative for living things (maybe viruses) to multiply and send their offspring into the future. So things change to make that more likely. Our drive to adapt has given us technological advances to help us live longer, on a more basic level fire helped us grow faster. We are primed to make use of what is around us, fire, and what we have, creativity and ingenuity. Why would other living things be different?
I like to but probably will end up anthropomorphizing stuff that shouldn’t be but bear with me. I don’t know if this qualifies as adaptation or evolution but dividing cells do the same thing we do albeit looking different. Bacteria gain resistance to antibiotics, plants creep into environments that previously were inhospitable, animals become city dwellers as humans expand. It is also true that cancers develop ways to grow in spite of treatment or lack of normal cell requirements.
In a past post I talked about the antiangiogenesis effects of itraconazole. Angiogenesis is the way cancer cells circumvent lack of blood flow. When you can make your own roads why wouldn’t you go wherever you wanted to? While not an adaptation I think, mTOR looks like it has helped cancer get a leg up in the body.
What is mTOR you ask? A konfusing kinase, don’t ask me to break that down. Mammalian target of rapamycin (an immune suppressing drug) or mTOR does a few things that aid cancer’s march. It inhibits the removal of defective or unused cells and cell stuffs. Think of this as the lack of proofreading during viral replication though by a different means. Not so much correction but rather taking the trash out.
Second, it regulates how cells proliferate. When over activated, it kicks that into overdrive. One of the ways this happens is through the angiogenesis I spoke of before. In the absence of nutrients mTOR causes angiogenesis in an attempt to bring said nutrients to the cell to prevent death. Which is great for normal cells but we want the cancer to die.
The best explanation I found that really broke it down Barney style was from a 2022 article in Frontiers in Aging Neuroscience, is that what happens when a book on the brain sits on the shelf for years? Anyways, here it is "In quiescent cells, the lack of growth factors and nutrients deactivates the mTOR pathway. Thus, the quiescent cell neither grows nor cycles. Despite such arrest, the cells retain their proliferative potential. Therefore, the re-addition of growth factors may cause reactivation of mTOR signaling, finally resulting in cell mass growth, cell cycle progression, mitosis, and cell proliferation." This is of course not the whole story but I'm trying here.
All that said, mTOR is a target for cancer treatments in an attempt to stop their expansions. There are many other things that affect how cancer grows and its aggressiveness and mTOR is only one. An interesting one non-the-less. I want to talk about others, especially hormone receptors. That was the original intent of this post until I heard someone talk about what mTOR does on a podcast. It's so cool how we are becoming better at identifying individual targets in diseases to go after, it is the way of the future. We all know that in general, tailor made objects are high quality, soon medicine may be tailor made. At least cancer medicine. Finesse.
Self serving plug: share this and the podcast. If you liked it, hated it, or want to educate me comment. I would love to hear from someone who knows what the hell they are talking about.
Love y'all.
References
Discovery of small molecule mechanistic target of rapamycin inhibitors as anti-aging and anti-cancer therapeutics in Frontiers in Aging Neuroscience by Chrienova et al., in 2022.
Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer from Nature Medicine by Thomas et al., in 2006.
Image of a cancer cell attaching to endothelial cells from an MIT article originating in Sengupta Lab
M(o)TOR of pseudo-hypoxic state in aging: Rapamycin to the rescue from Cell Cycle in 2014 by Leontieva & Blagosklonny.
mTOR: from growth signal integration to cancer, diabetes, and ageing by Zoncu et al., in Nature Reviews Molecular Cell Biology in 2011.
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