4 ms·

Cancer Weakness Discovered: New Method Pushes Cancer Cells into Remission

88 points by thedday 4y ago

adamredwoods 4y ago
Better article: https://datascience.cancer.gov/news-events/news/clim-data-science-approach-identifying-bystander-genes-cancer-precision-medicine https://datascience.cancer.gov/news-events/news/clim-data-sc... Actual article: https://www.nature.com/articles/s42255-022-00636-3 https://www.nature.com/articles/s42255-022-00636-3 Background on collateral lethality: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746004 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746004 CLIM on GitHub: https://github.com/DNagrathLab/CLIM/ https://github.com/DNagrathLab/CLIM/
FollowingTheDao 4y ago
If they think this will not have side affects in humans they are mistaken. MTFHD2 is needed in our mitochondria and blocking it will be worse than using methotrexate. There will be such a huge build of of NAD in the mitochondria things will go haywire. Maybe you all should stop eating so much folate so you do not get cancer in the first place: https://bmjopen.bmj.com/content/2/1/e000653 https://bmjopen.bmj.com/content/2/1/e000653 And what is weird is that these same oncologist were telling my father to take folate when he was dying of cancer.
- edgyquant 4y ago
  Telling people to stop eating a type of food doesn’t really help those who have cancer at the moment. How about we stop putting things in food until we can prove they don’t cause cancer
  - FollowingTheDao 4y ago
    > Telling people to stop eating a type of food doesn’t really help those who have cancer at the moment. I disagree. Telling to not eat folate will help them. If it was not true why are they giving you drugs to stop the folate cycle? https://www.nature.com/articles/s41392-022-01017-8 https://www.nature.com/articles/s41392-022-01017-8 https://www.nature.com/articles/bjc201711 https://www.nature.com/articles/bjc201711 Why continue to eat something that has been proven over and over again to drive tumor growth? It was LITERALLY how they found out that methotrexate worked. https://cen.acs.org/food/diet-change-course-cancer/100/i33 https://cen.acs.org/food/diet-change-course-cancer/100/i33 Indeed, the very first potent cancer drugs were based on the effects of cell metabolism. In the late 1940s, while pediatric pathologist Sidney Farber was treating children with anemia—a condition brought about because they had leukemia —he found that using folate (vitamin B9) could make the leukemia advance surprisingly quickly. That led him to successfully treat their leukemia with methotrexate, a drug that inhibits folate activity. Methotrexate is still widely used against cancer and several other diseases today. > How about we stop putting things in food until we can prove they don’t cause cancer. I agree, but that doesn’t really help those who have cancer at the moment.
  - deleted 4y ago
    [deleted]
  - throwaway12245 4y ago
    >Telling people to stop eating a type of food . Some claim a ketogenic diet may help. https://pubmed.ncbi.nlm.nih.gov/31399389/ https://pubmed.ncbi.nlm.nih.gov/31399389/ . "Major conclusions: The ketogenic diet probably creates an unfavorable metabolic environment for cancer cells and thus can be regarded as a promising adjuvant as a patient-specific multifactorial therapy."
    - capitainenemo 4y ago
      Intermittent fasting also triggers ketosis, possibly more effectively, has cancer prevention as one of the benefits and does not require diet changes (although they may help depending on what your diet was).
- tcj_phx 4y ago
  > Maybe you all should stop eating so much folate so you do not get cancer in the first place: https://bmjopen.bmj.com/content/2/1/e000653 https://bmjopen.bmj.com/content/2/1/e000653 Your link is about folic acid supplements, NOT folate. Folic acid is shelf-stable pro-vitamin that about 60-70% of the population is able to turn into Vitamin B9. The other 30-40% of the population are "poor methylators" who struggle with folic acid, or are harmed by folic acid. Poor methylators are on a spectrum, from 'not very good methylators' to 'very poor methylators'. I don't really grok biochemistry, but I think more people should avoid folic acid, and aim to get their nutrients from food. https://twitter.com/JamesKnochel/status/1595562181692907520 https://twitter.com/JamesKnochel/status/1595562181692907520 Edit: My understanding is that folic acid feeds the growth of inflammatory bacteria much more so than natural folate sources.
  - deleted 4y ago
    [deleted]
  - deleted 4y ago
    [deleted]
  - JPLeRouzic 4y ago
    I am a lay person but: * In the introduction of the linked BMJ article you can read: "Folic acid is a synthetic form of the essential B vitamin folate, also named folacin, pteroylglutamic acid or vitamin B9. Folic acid is in the human body converted to 5-methyltetrahydrofolate, which also is the form of folate found in dietary sources and is particularly abundant in vegetables, fruits and grains. " * In Wikipedia "folic acid" is redirected to "folate". https://en.wikipedia.org/wiki/Folic_acid https://en.wikipedia.org/wiki/Folic_acid In the "folate" WP page you find this sentence: "Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage."
  - stouset 4y ago
    > but I think more people should avoid folic acid And of course, there's people on the opposite end of the spectrum. For stroke survivors with certain kinds of vascular causes, folic acid supplementation is encouraged to reduce the risk of future strokes.
- thaumasiotes 4y ago
  > If they think this will not have side affects in humans they are mistaken. Sure, everything has side effects. This is a case where the side effects don't matter so much; people will put up with things in order to avoid dying a horrible death that they wouldn't tolerate in other circumstances.
- Gatsky 4y ago
  Folic acid supplementation reduces the toxicity of a chemotherapy drug called pemetrexed, used in lung cancer and mesothelioma. That could be why it was recommended. Sorry about your father.
  - FollowingTheDao 4y ago
    Thanks for the note about my father. But I want to show you how ridiculous it is for them to say that folic acid reduces the toxicity of PEMETREXED. The side effect of the drug is because it inhibits the folate cycle, which is why it stops cancer. So they want to give folate to someone who’s taking an anti-folate medication? Every oncologist I ask about this cannot give me a straight answer. The drug inhibit DHFR. When you take full late, you need the HFR to metabolize the folate. It’s just ridiculous and doctors have no understanding of basic nutritional biology. They were never taught in schools and they don’t care about it. Pemetrexed is chemically similar to folic acid and is in the class of chemotherapy drugs called folate antimetabolites. It works by inhibiting three enzymes used in purine and pyrimidine synthesis—thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase[16][17] (GARFT). By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells.
    - adamredwoods 4y ago
      The chemo cycle is designed to kill neoplasms, then to allow healthy cells recovery time. Oncologists don't want megaloblastic anemia, as that would lead to even more complications with vital organs. It looks like tests have been done, and vitamin supplements seem to be beneficial without changing efficacy: https://pubmed.ncbi.nlm.nih.gov/15117425/ https://pubmed.ncbi.nlm.nih.gov/15117425/ https://pubmed.ncbi.nlm.nih.gov/12722874/ https://pubmed.ncbi.nlm.nih.gov/12722874/
tinglymintyfrsh 4y ago
Considering the Western diet, human evolutionary history of constant near starvation, and how chemotherapy works, isn't cellular stress a near universal weakness of most neoplasmic cells?
- 0cf8612b2e1e 4y ago
  I only skimmed the article, but the entire thing seemed like some fluff to make a connection between machine learning and biology research. Cancer and genetic instability has been known for a very long time (hallmarks of cancer). Many energy/maintenance pathways are impaired or outright broken in cancer cells. Despite this knowledge, effectively targeting these “weaknesses” is far from trivial. Broken pathway does not a cancer cure make.
  - tinglymintyfrsh 4y ago
    Which makes sense. Chemo (limiting cell division, etc.) and/or starvation are "nuclear" options which rely on healthy cells weathering stress more so than cancer cells. Targeting (essentially assumed-to-be-novel) cancer cells specifically (say oncolytic viruses, pathway-blocking molecules or antibodies) seems extremely difficult without sheer luck of prior research matching particular tissues.
  - spfzero 4y ago
    But they actually did effectively target them. Six out of six complete remissions.
heisenbit 4y ago
This sounds very interesting. Being able to associate specific cancers with pathways worth dampening/shutting down may not just enable new medications but might allow us to leverage existing medications and engineer cocktails of medications for which we already know how they affect the cellular pathways.

88 points by thedday 4y ago

Better article: https://datascience.cancer.gov/news-events/news/clim-data-science-approach-identifying-bystander-genes-cancer-precision-medicine https://datascience.cancer.gov/news-events/news/clim-data-sc... Actual article: https://www.nature.com/articles/s42255-022-00636-3 https://www.nature.com/articles/s42255-022-00636-3 Background on collateral lethality: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746004 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746004 CLIM on GitHub: https://github.com/DNagrathLab/CLIM/ https://github.com/DNagrathLab/CLIM/

FollowingTheDao 4y ago

If they think this will not have side affects in humans they are mistaken. MTFHD2 is needed in our mitochondria and blocking it will be worse than using methotrexate. There will be such a huge build of of NAD in the mitochondria things will go haywire. Maybe you all should stop eating so much folate so you do not get cancer in the first place: https://bmjopen.bmj.com/content/2/1/e000653 https://bmjopen.bmj.com/content/2/1/e000653 And what is weird is that these same oncologist were telling my father to take folate when he was dying of cancer.

edgyquant 4y ago
Telling people to stop eating a type of food doesn’t really help those who have cancer at the moment. How about we stop putting things in food until we can prove they don’t cause cancer
- FollowingTheDao 4y ago
  > Telling people to stop eating a type of food doesn’t really help those who have cancer at the moment. I disagree. Telling to not eat folate will help them. If it was not true why are they giving you drugs to stop the folate cycle? https://www.nature.com/articles/s41392-022-01017-8 https://www.nature.com/articles/s41392-022-01017-8 https://www.nature.com/articles/bjc201711 https://www.nature.com/articles/bjc201711 Why continue to eat something that has been proven over and over again to drive tumor growth? It was LITERALLY how they found out that methotrexate worked. https://cen.acs.org/food/diet-change-course-cancer/100/i33 https://cen.acs.org/food/diet-change-course-cancer/100/i33 Indeed, the very first potent cancer drugs were based on the effects of cell metabolism. In the late 1940s, while pediatric pathologist Sidney Farber was treating children with anemia—a condition brought about because they had leukemia —he found that using folate (vitamin B9) could make the leukemia advance surprisingly quickly. That led him to successfully treat their leukemia with methotrexate, a drug that inhibits folate activity. Methotrexate is still widely used against cancer and several other diseases today. > How about we stop putting things in food until we can prove they don’t cause cancer. I agree, but that doesn’t really help those who have cancer at the moment.
- deleted 4y ago
  [deleted]
- throwaway12245 4y ago
  >Telling people to stop eating a type of food . Some claim a ketogenic diet may help. https://pubmed.ncbi.nlm.nih.gov/31399389/ https://pubmed.ncbi.nlm.nih.gov/31399389/ . "Major conclusions: The ketogenic diet probably creates an unfavorable metabolic environment for cancer cells and thus can be regarded as a promising adjuvant as a patient-specific multifactorial therapy."
  - capitainenemo 4y ago
    Intermittent fasting also triggers ketosis, possibly more effectively, has cancer prevention as one of the benefits and does not require diet changes (although they may help depending on what your diet was).
tcj_phx 4y ago
> Maybe you all should stop eating so much folate so you do not get cancer in the first place: https://bmjopen.bmj.com/content/2/1/e000653 https://bmjopen.bmj.com/content/2/1/e000653 Your link is about folic acid supplements, NOT folate. Folic acid is shelf-stable pro-vitamin that about 60-70% of the population is able to turn into Vitamin B9. The other 30-40% of the population are "poor methylators" who struggle with folic acid, or are harmed by folic acid. Poor methylators are on a spectrum, from 'not very good methylators' to 'very poor methylators'. I don't really grok biochemistry, but I think more people should avoid folic acid, and aim to get their nutrients from food. https://twitter.com/JamesKnochel/status/1595562181692907520 https://twitter.com/JamesKnochel/status/1595562181692907520 Edit: My understanding is that folic acid feeds the growth of inflammatory bacteria much more so than natural folate sources.
- deleted 4y ago
  [deleted]
- deleted 4y ago
  [deleted]
- JPLeRouzic 4y ago
  I am a lay person but: * In the introduction of the linked BMJ article you can read: "Folic acid is a synthetic form of the essential B vitamin folate, also named folacin, pteroylglutamic acid or vitamin B9. Folic acid is in the human body converted to 5-methyltetrahydrofolate, which also is the form of folate found in dietary sources and is particularly abundant in vegetables, fruits and grains. " * In Wikipedia "folic acid" is redirected to "folate". https://en.wikipedia.org/wiki/Folic_acid https://en.wikipedia.org/wiki/Folic_acid In the "folate" WP page you find this sentence: "Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage."
- stouset 4y ago
  > but I think more people should avoid folic acid And of course, there's people on the opposite end of the spectrum. For stroke survivors with certain kinds of vascular causes, folic acid supplementation is encouraged to reduce the risk of future strokes.
thaumasiotes 4y ago
> If they think this will not have side affects in humans they are mistaken. Sure, everything has side effects. This is a case where the side effects don't matter so much; people will put up with things in order to avoid dying a horrible death that they wouldn't tolerate in other circumstances.
Gatsky 4y ago
Folic acid supplementation reduces the toxicity of a chemotherapy drug called pemetrexed, used in lung cancer and mesothelioma. That could be why it was recommended. Sorry about your father.
- FollowingTheDao 4y ago
  Thanks for the note about my father. But I want to show you how ridiculous it is for them to say that folic acid reduces the toxicity of PEMETREXED. The side effect of the drug is because it inhibits the folate cycle, which is why it stops cancer. So they want to give folate to someone who’s taking an anti-folate medication? Every oncologist I ask about this cannot give me a straight answer. The drug inhibit DHFR. When you take full late, you need the HFR to metabolize the folate. It’s just ridiculous and doctors have no understanding of basic nutritional biology. They were never taught in schools and they don’t care about it. Pemetrexed is chemically similar to folic acid and is in the class of chemotherapy drugs called folate antimetabolites. It works by inhibiting three enzymes used in purine and pyrimidine synthesis—thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase[16][17] (GARFT). By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells.
  - adamredwoods 4y ago
    The chemo cycle is designed to kill neoplasms, then to allow healthy cells recovery time. Oncologists don't want megaloblastic anemia, as that would lead to even more complications with vital organs. It looks like tests have been done, and vitamin supplements seem to be beneficial without changing efficacy: https://pubmed.ncbi.nlm.nih.gov/15117425/ https://pubmed.ncbi.nlm.nih.gov/15117425/ https://pubmed.ncbi.nlm.nih.gov/12722874/ https://pubmed.ncbi.nlm.nih.gov/12722874/

tinglymintyfrsh 4y ago

Considering the Western diet, human evolutionary history of constant near starvation, and how chemotherapy works, isn't cellular stress a near universal weakness of most neoplasmic cells?

0cf8612b2e1e 4y ago
I only skimmed the article, but the entire thing seemed like some fluff to make a connection between machine learning and biology research. Cancer and genetic instability has been known for a very long time (hallmarks of cancer). Many energy/maintenance pathways are impaired or outright broken in cancer cells. Despite this knowledge, effectively targeting these “weaknesses” is far from trivial. Broken pathway does not a cancer cure make.
- tinglymintyfrsh 4y ago
  Which makes sense. Chemo (limiting cell division, etc.) and/or starvation are "nuclear" options which rely on healthy cells weathering stress more so than cancer cells. Targeting (essentially assumed-to-be-novel) cancer cells specifically (say oncolytic viruses, pathway-blocking molecules or antibodies) seems extremely difficult without sheer luck of prior research matching particular tissues.
- spfzero 4y ago
  But they actually did effectively target them. Six out of six complete remissions.

heisenbit 4y ago

This sounds very interesting. Being able to associate specific cancers with pathways worth dampening/shutting down may not just enable new medications but might allow us to leverage existing medications and engineer cocktails of medications for which we already know how they affect the cellular pathways.