6 ms·

Since you were a cancer researcher in a previous life, may I ask you a question I thought of commenting on another's comment? If cancer cells have high metabol

Since you were a cancer researcher in a previous life, may I ask you a question I thought of commenting on another's comment? If cancer cells have high metabolic requirements, couldn't you attack them by: 1. lowering the caloric intake of the patient 2. Making the glucose the patient intakes mildly radioactive, say with a beta or an alpha emitter [1]. As the patient is strictly kept on a low caloric diet, the radioactive glucose is consumed and expelled quickly (i.e. doesn't accumulate in the adipose (?) tissue). Not so radioactive that the person is harmed but radioactive enough to pack an extra punch to the metabolically starved, and therefore stressed, cancer cells (who are drawing more of the glucose to themselves). That should target cancer more specifically, and I guess it can be done in tandem with other techniques. Is something similar done? I know that's how cancer is imaged, and the way I see it (I studied optics in a previous life) if you can image it, you should be able to destroy it. [1] Say replacing the hydrogens in glucose with tritium. Hydrogen hopping will ensure that the water produced by metabolizing the sugar is homogeneously mixed, and therefore expelled with all the water loss mechanisms. According to wikipedia, TO2 has a half life of 12 days. I'd imagine you can lower that by pumping fluids into the patient.

dnautics 6y ago
[1] Say replacing the hydrogens in glucose with tritium That's part of the problem. Think you can come up with a synthesis of glucose that replaces the nonlabile hydrogens with tritium, is doable on the days scale, repurifiable for human consumption and mass producable on-site at a hospital? For reference ($900/20Ci): https://www.perkinelmer.com/product/glucose-d-3-3h-hplc-purified-net331c250uc https://www.perkinelmer.com/product/glucose-d-3-3h-hplc-puri...
- eutectic 6y ago
  What about an enzymatic synthesis? Or even partial biosynthesis.
- smartscience 6y ago
  I'd be willing to have a crack at this if I thought it could help (my background is in nuclear methods for materials characterisation). But I've a feeling that the difference in uptake between cancerous and normal tissue might not be large enough to make this especially useful. Fluorine-18 labelled glucose is used in PET imaging, but not for treatment as far as I'm aware. On the other hand, if a compound can be found that is more selective for the cancer in question, making it radioactive may offer a further improvement.
  - whatshisface 6y ago
    Isotope labeling for imaging requires only a low isotope purity. One radioactive glucose in a vast sea of normal glucose is just fine, because as I'm sure you know the energies of the emitted particles make a very distinct marker.
- IfOnlyYouKnew 6y ago
  Just grow some sprouts in it? (Not an endorsement of the idea)
phkahler 6y ago
The high metabolic rate is used. Some forms of chemotherapy kill cells that replicate quickly. That's why hair falls out and patients puke - the gut lining replicates quickly. At least that's my understanding. I'm not in the field.
aficiomaquinas 6y ago
There is a very interesting book around the metabolic route for treating cancer. It's called "Starving cancer" by Jane McLelland. It talks about using over the counter drugs and supplements that have been studied for their metabolic blocking properties for cancer, as well as changing the diet to reduce as much as possible the nutrients that cancer craves the most according to their metabolic phenotype. Most of the times it's glucose or glutamine, but the trick is to block as many metabolic pathways using the drugs so that mutation is prevented. Most of these drugs have their patents expired and are quite cheap. The author had a very aggressive form of cancer with less than 5% statistic survival rate and were able to survive and go back to NED (no evidence of disease). It's not exactly a substitute for standard therapy such as chemo, but there's many people who also went to NED just with her protocol. I tried this back when I had cancer, and even though my survival rate was very high just on standard care, my tumor markers went way down almost to normal on the first cycle combined with Jane's protocol. Unfortunately, the cancer industry and pharmaceutical industry won't really invest much money on clinical trials for expired patent, or even existing drugs in their portfolio. There are a couple of independent clinical trials going on, so far, with good results AFAIC. Another very controversial, but interesting treatment for cancer that will probably never see the light is Chlorine Dioxide. And don't you dare write that on Facebook or YouTube because it'll be outright banned or deleted for "spreading misinformation". I have friends and persons I know that went to NED just on chlorine dioxide and diet. Having used it myself for many months with no negative effects, and, after chemo, I can't help but cringe every time someone tells me that it's "very toxic". Oh lord, you should have seen what chemo was like. Now, that was toxic.
- IfOnlyYouKnew 6y ago
  If something is flagged by YouTube, it must be a really bad idea. Chlorine isn’t too bad in terms of toxicity, or it wouldn’t be added to drinking water and freely sold for all sorts of purposes. But there’s absolutely no reason to ingest it (or any other route of administration). I guess it’s exactly because of it’s ubiquity that those of a conspiratorial mindset like it so much: it fits with the idea that there are obvious and easy answers suppressed by that mighty cabal of Bill Gates/Soros/some other Jews.
IfOnlyYouKnew 6y ago
Low-carb is a thing/fad/potentially useful practice among patients. As to Radioactivity, I’m not sure if your model would work: higher usage does not necessarily mean “more contact with”. Does the fish that drinks more have more exposure to water than his friend? That said, radioactivity is obviously used, because cells at the proliferation stage are specifically susceptible to it. The same is true for most chemotherapy, I. e. they target the mechanisms of cell division.
twic 6y ago
> Making the glucose the patient intakes mildly radioactive The carbon and oxygen in glucose used as fuel doesn't stay in the cell - it becomes lactic acid (or carbon dioxide and water), which leaves the cell. You could make a weaponised version of something which does get retained in the cancer cell. For example, nucleosides, which are the raw material for DNA, and which are needed in volume to support cancer cells' rapid proliferation. These drugs are called nucleoside analogues, and are used to treat cancer and viruses: https://en.wikipedia.org/wiki/Gemcitabine https://en.wikipedia.org/wiki/Gemcitabine
gamblor956 6y ago
If cancer cells have high metabolic requirements, couldn't you attack them by:... The keto diet is actually recommended for certain types of cancer patients for this reason. While almost all human body cells can adjust to using ketones, most types of cancer cells cannot.
wittyreference 6y ago
Great questions. 1. We do attempt to attack cancers by reducing their available energy. That's why, at one point, a major field of research in cancer therapeutics was interfering with angiogenesis, because cancers will secrete messengers that help grow them dedicated (if crappy, low-quality) blood vessels. The issue with "starving" them more starkly is that they're very good at getting a share (e.g., forcing the body to supply them with blood vessels), so you're going to be hitting other labile tissues as fast or faster (skin, GI mucosa, blood and immune cells.) Another way of targeting their rapid metabolism is pointing our therapy at cells with high replication rates. A number of our cancer therapeutics are aimed directly at cells that are currently replicating, which should selectively hit cancer cells (though again, it hits skin, GI mucosa, blood and immune cells, etc. because they're also high-turnover cells.) We use methotrexate to interfere with DNA synthesis, thus reducing the rate of replication altogether (in cancer cells, as well as.... above). The problem is, besides the dose-limiting toxicities of all of these things (because targeting metabolism hits all high-metabolism cells), is that cancer cells are really good at developing resistances. So, for instance, if you starve them of blood supply, they'll switch to anaerobic metabolism of glucose. If you starve them of glucose, well, you can't really - I'll discuss that below. If you give them methotrexate or other nasty drugs, they alter the cells' native drug-efflux pumps to target those drugs better and pump them right out of the cell. Cancer cells have a broken mechanism for protecting DNA - the result is really high rates of cell death among cancer cells, and also really rapid evolution. In terms of starving cells of glucose: glucose is the least common denominator of cellular metabolism. It's the primary food source for the brain. Different cells have different receptors for absorbing it, with different levels of affinity. If you're running low, pretty much every cell in the body that can will kick up metabolic products to the liver to turn into glucose it can share with the bloodstream - because the best receptors in the bloodstream for picking up glucose belong to the brain. You'll starve, or poison, the brain long before you manage to starve out a cancer. (Yes, Ketone bodies are a thing, but that happens alongside your body mobilizing everything it can to feed the brain, not instead of.) We also can't 'see' all the tumor. The way cancers actually develop is you have an abnormal cell A, which grows into a tiny nest. These are below detection in any practical clinical way, and we don't want to treat them because they're ridiculously common - your immune system wipes them up. If we tried to detect and treat them all, we'd kill everyone with side effects long before we prevented a fatal cancer. Out of the bunches of these that develop and die, or develop and go permanently quiet, one gets active enough to start seeding tumor cells into the blood stream. Most of those cells will die, too, because blood is rough for cells not built to withstand it. Most of these are going to be undetectable in any way, and do nothing to people. (Every time I say something is undetectable, I mean "Except for high precision laboratory experiments used to detect just such things"). Eventually a tiny pre-pre-tumor will start seeding cells into the blood stream that can survive the blood. These will get seeded effing everywhere. Most of these are permanently quiescent and do nothing, ever. They exist at the level of single cells - we can't see them. They don't do anything, metabolic activity very low, so we can't target them. Once in a blue moon you get one seeded that is actually metabolically highly active. Or maybe it mutates into metabolic activity later. Most of those die. Once in a blue moon, one of these will live enough to start replicating for real. Most of those get wiped out. And once in a blue moon, they start replicating for real, and develop immune evasion, and you have something that becomes a cancer, maybe. Or it gets triggered by something external and becomes a cancer. There's a "seed and soil" element here. It'll often start seeding back into the blood stream. By the time you have a detectable mass, your entire body has been seeded with these cells, most of them both un-image-able and un-selectively-treatable. Luckily, the overwhelming majority of these cells - lots of nines - won't do jack. Of the trillions that will seed your body, if we stimulate them just right, you might get a couple of new tumors, or none at all. We know this because we learned that tumors benefit from circulating inflammatory markers early in modern oncology. When a surgeon took out a tumor, not infrequently, a patient would come in a year later with a new one or two that weren't previously detectable. We eventually learned that the inflammatory growth signals that come with surgical trauma can provoke an otherwise sleepy tumor cell into metabolic activity. Which is a roundabout way of saying "cancers are more metabolically varied than the late, aggressive stage of the process we usually refer to as 'cancer' would suggest." That being said, if you could inject something directly into the tumor (rather than the bloodstream would prioritize sending said poison pill glucose to the brain or liver) and take advantage of its metabolism, that would be great. We do kind of do that: we implant radioactive pellets directly, with the added benefit that we know it won't affect much tissue outside of the immediate area. I hope my answer was actually useful in providing some biological context? I'm afraid I might have just word-vomited instead of being helpful.
scythe 6y ago
>Not so radioactive that the person is harmed but radioactive enough to pack an extra punch to the metabolically starved, and therefore stressed, cancer cells (who are drawing more of the glucose to themselves). Tritium will be transferred to proteins and retained in the body. A low-calorie diet won't help: when the glucose enters the citric acid cycle, the 3H will end up everywhere. 18FDG, used for PET, is also concentrated in the kidneys and bladder, ruling it out for therapy. If it were that easy to find something uptaken only by tumors, we'd be using it. In brachytherapy, we do something like this, except we put a solid radiation source inside the tumor. Nonetheless, the treatment has serious side effects.

dnautics 6y ago

[1] Say replacing the hydrogens in glucose with tritium That's part of the problem. Think you can come up with a synthesis of glucose that replaces the nonlabile hydrogens with tritium, is doable on the days scale, repurifiable for human consumption and mass producable on-site at a hospital? For reference ($900/20Ci): https://www.perkinelmer.com/product/glucose-d-3-3h-hplc-purified-net331c250uc https://www.perkinelmer.com/product/glucose-d-3-3h-hplc-puri...

eutectic 6y ago
What about an enzymatic synthesis? Or even partial biosynthesis.
smartscience 6y ago
I'd be willing to have a crack at this if I thought it could help (my background is in nuclear methods for materials characterisation). But I've a feeling that the difference in uptake between cancerous and normal tissue might not be large enough to make this especially useful. Fluorine-18 labelled glucose is used in PET imaging, but not for treatment as far as I'm aware. On the other hand, if a compound can be found that is more selective for the cancer in question, making it radioactive may offer a further improvement.
- whatshisface 6y ago
  Isotope labeling for imaging requires only a low isotope purity. One radioactive glucose in a vast sea of normal glucose is just fine, because as I'm sure you know the energies of the emitted particles make a very distinct marker.
IfOnlyYouKnew 6y ago
Just grow some sprouts in it? (Not an endorsement of the idea)

phkahler 6y ago

The high metabolic rate is used. Some forms of chemotherapy kill cells that replicate quickly. That's why hair falls out and patients puke - the gut lining replicates quickly. At least that's my understanding. I'm not in the field.

aficiomaquinas 6y ago

There is a very interesting book around the metabolic route for treating cancer. It's called "Starving cancer" by Jane McLelland. It talks about using over the counter drugs and supplements that have been studied for their metabolic blocking properties for cancer, as well as changing the diet to reduce as much as possible the nutrients that cancer craves the most according to their metabolic phenotype. Most of the times it's glucose or glutamine, but the trick is to block as many metabolic pathways using the drugs so that mutation is prevented. Most of these drugs have their patents expired and are quite cheap. The author had a very aggressive form of cancer with less than 5% statistic survival rate and were able to survive and go back to NED (no evidence of disease). It's not exactly a substitute for standard therapy such as chemo, but there's many people who also went to NED just with her protocol. I tried this back when I had cancer, and even though my survival rate was very high just on standard care, my tumor markers went way down almost to normal on the first cycle combined with Jane's protocol. Unfortunately, the cancer industry and pharmaceutical industry won't really invest much money on clinical trials for expired patent, or even existing drugs in their portfolio. There are a couple of independent clinical trials going on, so far, with good results AFAIC. Another very controversial, but interesting treatment for cancer that will probably never see the light is Chlorine Dioxide. And don't you dare write that on Facebook or YouTube because it'll be outright banned or deleted for "spreading misinformation". I have friends and persons I know that went to NED just on chlorine dioxide and diet. Having used it myself for many months with no negative effects, and, after chemo, I can't help but cringe every time someone tells me that it's "very toxic". Oh lord, you should have seen what chemo was like. Now, that was toxic.

IfOnlyYouKnew 6y ago
If something is flagged by YouTube, it must be a really bad idea. Chlorine isn’t too bad in terms of toxicity, or it wouldn’t be added to drinking water and freely sold for all sorts of purposes. But there’s absolutely no reason to ingest it (or any other route of administration). I guess it’s exactly because of it’s ubiquity that those of a conspiratorial mindset like it so much: it fits with the idea that there are obvious and easy answers suppressed by that mighty cabal of Bill Gates/Soros/some other Jews.

IfOnlyYouKnew 6y ago

Low-carb is a thing/fad/potentially useful practice among patients. As to Radioactivity, I’m not sure if your model would work: higher usage does not necessarily mean “more contact with”. Does the fish that drinks more have more exposure to water than his friend? That said, radioactivity is obviously used, because cells at the proliferation stage are specifically susceptible to it. The same is true for most chemotherapy, I. e. they target the mechanisms of cell division.

twic 6y ago

> Making the glucose the patient intakes mildly radioactive The carbon and oxygen in glucose used as fuel doesn't stay in the cell - it becomes lactic acid (or carbon dioxide and water), which leaves the cell. You could make a weaponised version of something which does get retained in the cancer cell. For example, nucleosides, which are the raw material for DNA, and which are needed in volume to support cancer cells' rapid proliferation. These drugs are called nucleoside analogues, and are used to treat cancer and viruses: https://en.wikipedia.org/wiki/Gemcitabine https://en.wikipedia.org/wiki/Gemcitabine

gamblor956 6y ago

If cancer cells have high metabolic requirements, couldn't you attack them by:... The keto diet is actually recommended for certain types of cancer patients for this reason. While almost all human body cells can adjust to using ketones, most types of cancer cells cannot.

wittyreference 6y ago

Great questions. 1. We do attempt to attack cancers by reducing their available energy. That's why, at one point, a major field of research in cancer therapeutics was interfering with angiogenesis, because cancers will secrete messengers that help grow them dedicated (if crappy, low-quality) blood vessels. The issue with "starving" them more starkly is that they're very good at getting a share (e.g., forcing the body to supply them with blood vessels), so you're going to be hitting other labile tissues as fast or faster (skin, GI mucosa, blood and immune cells.) Another way of targeting their rapid metabolism is pointing our therapy at cells with high replication rates. A number of our cancer therapeutics are aimed directly at cells that are currently replicating, which should selectively hit cancer cells (though again, it hits skin, GI mucosa, blood and immune cells, etc. because they're also high-turnover cells.) We use methotrexate to interfere with DNA synthesis, thus reducing the rate of replication altogether (in cancer cells, as well as.... above). The problem is, besides the dose-limiting toxicities of all of these things (because targeting metabolism hits all high-metabolism cells), is that cancer cells are really good at developing resistances. So, for instance, if you starve them of blood supply, they'll switch to anaerobic metabolism of glucose. If you starve them of glucose, well, you can't really - I'll discuss that below. If you give them methotrexate or other nasty drugs, they alter the cells' native drug-efflux pumps to target those drugs better and pump them right out of the cell. Cancer cells have a broken mechanism for protecting DNA - the result is really high rates of cell death among cancer cells, and also really rapid evolution. In terms of starving cells of glucose: glucose is the least common denominator of cellular metabolism. It's the primary food source for the brain. Different cells have different receptors for absorbing it, with different levels of affinity. If you're running low, pretty much every cell in the body that can will kick up metabolic products to the liver to turn into glucose it can share with the bloodstream - because the best receptors in the bloodstream for picking up glucose belong to the brain. You'll starve, or poison, the brain long before you manage to starve out a cancer. (Yes, Ketone bodies are a thing, but that happens alongside your body mobilizing everything it can to feed the brain, not instead of.) We also can't 'see' all the tumor. The way cancers actually develop is you have an abnormal cell A, which grows into a tiny nest. These are below detection in any practical clinical way, and we don't want to treat them because they're ridiculously common - your immune system wipes them up. If we tried to detect and treat them all, we'd kill everyone with side effects long before we prevented a fatal cancer. Out of the bunches of these that develop and die, or develop and go permanently quiet, one gets active enough to start seeding tumor cells into the blood stream. Most of those cells will die, too, because blood is rough for cells not built to withstand it. Most of these are going to be undetectable in any way, and do nothing to people. (Every time I say something is undetectable, I mean "Except for high precision laboratory experiments used to detect just such things"). Eventually a tiny pre-pre-tumor will start seeding cells into the blood stream that can survive the blood. These will get seeded effing everywhere. Most of these are permanently quiescent and do nothing, ever. They exist at the level of single cells - we can't see them. They don't do anything, metabolic activity very low, so we can't target them. Once in a blue moon you get one seeded that is actually metabolically highly active. Or maybe it mutates into metabolic activity later. Most of those die. Once in a blue moon, one of these will live enough to start replicating for real. Most of those get wiped out. And once in a blue moon, they start replicating for real, and develop immune evasion, and you have something that becomes a cancer, maybe. Or it gets triggered by something external and becomes a cancer. There's a "seed and soil" element here. It'll often start seeding back into the blood stream. By the time you have a detectable mass, your entire body has been seeded with these cells, most of them both un-image-able and un-selectively-treatable. Luckily, the overwhelming majority of these cells - lots of nines - won't do jack. Of the trillions that will seed your body, if we stimulate them just right, you might get a couple of new tumors, or none at all. We know this because we learned that tumors benefit from circulating inflammatory markers early in modern oncology. When a surgeon took out a tumor, not infrequently, a patient would come in a year later with a new one or two that weren't previously detectable. We eventually learned that the inflammatory growth signals that come with surgical trauma can provoke an otherwise sleepy tumor cell into metabolic activity. Which is a roundabout way of saying "cancers are more metabolically varied than the late, aggressive stage of the process we usually refer to as 'cancer' would suggest." That being said, if you could inject something directly into the tumor (rather than the bloodstream would prioritize sending said poison pill glucose to the brain or liver) and take advantage of its metabolism, that would be great. We do kind of do that: we implant radioactive pellets directly, with the added benefit that we know it won't affect much tissue outside of the immediate area. I hope my answer was actually useful in providing some biological context? I'm afraid I might have just word-vomited instead of being helpful.

scythe 6y ago

>Not so radioactive that the person is harmed but radioactive enough to pack an extra punch to the metabolically starved, and therefore stressed, cancer cells (who are drawing more of the glucose to themselves). Tritium will be transferred to proteins and retained in the body. A low-calorie diet won't help: when the glucose enters the citric acid cycle, the 3H will end up everywhere. 18FDG, used for PET, is also concentrated in the kidneys and bladder, ruling it out for therapy. If it were that easy to find something uptaken only by tumors, we'd be using it. In brachytherapy, we do something like this, except we put a solid radiation source inside the tumor. Nonetheless, the treatment has serious side effects.