Akt, mTOR, NFκB TGFβ... What in the heck does all of this mean?
With Jane McClelland's publication of How to Starve Cancer, suddenly lay people started buzzing about cancer "pathways" and what they mean for our own cancer care.
Such a complex topic leads to a lot of confusion, so today, I wanted to talk a little bit about what this all means and how it can help you in discussions with your doctors.
First, I want to point out that you are not going to achieve the ability to treat yourself holistically without some major risks. Do people do it? Yes, absolutely. And sometimes they have success. However, a cancer patient is scared, overwhelmed, and short on time and knowledge. That's a recipe for some big mistakes.
I understand that many men and women fall back on self-treatment because conventional treatment either fails them or is impossible for whatever reason. I also understand that qualified integrative and holistic doctors are often expensive and hard to come by. So, I don't want to persuade or dissuade anyone from whatever they feel suits their needs best. Each situation is different, so I really have to reiterate that this blog is for educational purposes only. I'm not making any claims about what treatments will or will not work for your situation, nor am I making any suggestions about what individuals should or should not do.
Well, with the exception of the general advice that you could probably use more kale and exercise in your life. But that's all of us, right?
Okay, so what is a cancer pathway, exactly?
I kind of hate that term. I prefer calling them "biological mechanisms." Believe it or not, "pathways" is actually the technical term, but I don't know why it was picked. It means a signaling pathway. To me, "signaling pathway" makes it sound all pie-in-the-sky like I'm going to tell you the only way you can survive this is if you stop showering and eat locusts or something.
By all means, if you want to eat locusts, go ahead. Just make sure they're organic.
For the non-invertebrate-munchers of us, though, I want you to understand that this is a legitimate thing.
There are several processes that allow cancer to thrive. Caner cells grow nonstop, they have an altered metabolism, they lose the ability to receive signals from other cells and growth suppressors, they are hard to kill, they make babies that are hard to kill, they recruit other systems to supply them with their needs, and they can evade our immune systems. The scariest, though, is that they spread to other tissues. As tumors, or clumps of these cancer cells, grow, their daughter cells tend to accumulate more and more mutations, leading to a less differentiated cancer cell with more issues. (Less differentiated means that it looks less like the original cell type. This is how we sometimes get cancers of unknown origins. Those suckers have transformed more thoroughly than a mogwai at a buffet after midnight. Nobody knows where they came from.)
According to Mary Crowley Cancer Research, all of this stuff is driven by only twelve "pathways," however many lay people refer to linked biological processes and treatment targets- or stops along these pathways- as pathways, too. For example, the PARP family of proteins is only one target for affecting the "Genome instability and mutation" pathway, as defined by the Mary Crowley Cancer Research website, but many lay people call the PARP family a "pathway" itself. From what I understand, that's not really accurate.
Because of this, I think us patients struggle to have a coherent technical conversation with our doctors. We're kind of speaking different languages.
For the purpose of this blog, I'll try to remember to call them by appropriate names, but I probably won't. I'm no oncologist! Feel free to school me with your superior wisdom if you must.
So, what are these pathways... or mechanisms... or targets?
Well, in short, they're the gas for the cancer. They're the different things that have to happen in the body for the cancer to keep going. For example, angiogenesis is driven by the Vascular Endothelial Growth Factor, or VEGF. We want to inhibit VEGF so that tumors don't get all the nutrients they want to rob from our bodies. We inhibit VEGF with drugs like Avastin.
A down side to this is that we don't have the pharmaceuticals to affect every pathway. In fact, we have very few drugs to inhibit very few pathways. And the really awful part is that we don't necessarily know which ones are going to be effective for getting rid of our cancer, either.
For example, in ovarian cancer we know that the PARP inhibitors tend to work really well for women with a BRCA mutation either in their inherited DNA or their tumors. They are hit or miss for other women, though. Many women take PARP inhibitors and they have recurrences on them.
Researchers are learning more and more about which specific mutations are best controlled by which pathway and they're trying to develop drugs to work on them, but they just aren't there completely yet. In fact, the p53 mutation is present in over 90% of ovarian cancers and over half of all cancers in general. There is no current targeted treatment for that mutation.
Womp, womp.
However, there is good news.
Are you ready for the good news? I'm ready for the good news. This post has been kind of a downer so far. The good news is, we do know of natural supplements, spices, foods, and lifestyle habits which help support normal function of these pathways.
Obviously, we'd love it if we have a medication which we could take to cure us of cancer, but until that happens, we have many natural supports available to us. That's why understanding the basics of the pathways and what works on them is essential for a frank and detailed conversation with your care providers. If you go into your doctor's office and say, "Hey, can I take a curcumin supplement?" the answer may be quite different than in if you broach the topic with, "Hey, these are the studies I have seen. I've read that curcumin works on WNT, BCL-2, MEK, mTOR/P13K/Akt, STAT3, EGFR, VEGF, MMP-2, PGE-2, and TGFβ. What are your thoughts on me taking it?"
Remember that your doctors don't know your level of education on the topic of cancer. They don't know your mental capacity to deal with a lot of new information. They also don't know your level of commitment.
Cancer patients are notorious for saying things like, "Eh. Why change my diet? I'll probably die from this anyway," or "I don't really see the point in taking any supplements. My doctor will give me anything that will help." If you're on this blog, I'm going to assume that you're plans are to beat this and you're willing to do whatever it takes, but we are not the standard in cancer care and your doctor can't waste time on people who are half-heartedly trying to change. So, do some homework so you can actually have those discussions. While looking at ways to target these pathways, it would be awesome if we had all of them in nice flow charts which would help us understand how they interact. You can find a smattering of them online, and they are available in oncology textbooks. But you probably don't need to know all of those details unless you're a doctor using actual pharmaceuticals to treat someone. When you're using natural sources to help support these pathways, it's less important to know whether you are targeting a pathway at a bottleneck (ie- the most effective place to stop a process), or whether it only inhibits a portion of the process. That's because natural supplements and foods are typically gentle, safe, and cheap in comparison with pharmaceutical drugs. You do need to know which pathways are affected by which supplements, though, and which ones are most likely to be in chaos in your particular cancer. You also need to know what supplements might interact with your medications.
That should be a relief because it's a lot easier to research and figure out which supplements support healthy function of specific pathways than it is to understand the downstream effects of every single process, protein, or enzyme in your body. A good integrative doctor will also be able to tell you what interactions to beware of. I hope that is a helpful introduction to the whole concept of cancer pathways. Be sure to take a look at my must read cancer booklist for books on detailed research, and of course, share any great resources for new cancer patients in the comments!
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Photo credit: Uday Mittal via Unsplash
https://www.marycrowley.org/groundbreaking-research/cancer-pathways/
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