5 ms·

All this genetic diversity seems daunting at first but I think it is also indicative of something that gives me great hope. Cancer isn't like a virus or pathog

All this genetic diversity seems daunting at first but I think it is also indicative of something that gives me great hope. Cancer isn't like a virus or pathogen that has evolved to avoid it our immune systems and treatments as it passes from individual. It is a degenerative state of the same system that produces healthy cells and fertile humans. It is genetically very diverse. Part of this is because cancers cells often have mesed up chromosomal replication which produces more variability. Part of this may be because numerous genetic variations can have similar effects because they effect the same gene or network of genes. As the author alludes to at the end of the paper, there are a number of things a tumor must do to be successful. These include avoiding the immune system, avoiding programed cell death, recruiting blood vessels/nutrients etc. There has been lots of really promising research in the last few years that looks at analyzing and targeting the pathways that control these things. Further as projects like the the Cancer Genome Atlas (which I work on as a Software Engineer) produce terabytes of data about cancer, we are able to apply modern data analysis to better understand the system, hopefully discovering what separates the biochemical state of an aggressive cancer from one the body handles without issue which will hopefully lead to some novel drug targets.

jimmyvanhalen 15y ago
Here's something interesting about a common chemical compound called Dichloroacetic acid (DCA). Big pharma is ignoring it since it can't be patented (because it's so common). Cancer cells change the way they metabolize oxygen in a way that promotes their survival. In laboratory studies of isolated cancer cells grown in tissue culture, DCA restores the original metabolism, and promotes their self-destruction. This has led to the use of DCA for treating cancer, by individuals experimenting with it themselves, by doctors administering it to patients as a non-approved drug, by scientists testing it in cancer tissue cultures in cell culture and in mice, and in human Phase II studies. DCA has improved certain biochemical parameters, but it has not demonstrated improved survival. Cancer cells generally express increased glycolysis, because they rely on anaerobic respiration that occurs in the cytosol (lactic acid fermentation) rather than oxidative phosphorylation in the mitochondria for energy (the Warburg effect), as a result of hypoxia that exists in tumors and malfunctioning mitochondria. [9] [10] Usually dangerously damaged cells kill themselves via apoptosis, a mechanism of self-destruction that involves mitochondria, but this mechanism fails in cancer cells. A phase I study published in January 2007 by researchers at the University of Alberta, who had tested DCA on human[11] cancer cells grown in mice, found that DCA restored mitochondrial function, thus restoring apoptosis, allowing cancer cells to self-destruct and shrink the tumor.[12] These results received extensive media attention, beginning with an article in New Scientist titled "Cheap, ‘safe’ drug kills most cancers".[11] Subsequently, the American Cancer Society and other medical organizations have received a large volume of public interest and questions regarding DCA.[13] Clinical trials in humans with cancer have not been conducted in the USA and are not yet final in Canada, emphasizing the need for caution in interpreting the preliminary results.[13][14] http://en.wikipedia.org/wiki/Dichloroacetic_acid http://en.wikipedia.org/wiki/Dichloroacetic_acid
- polyfractal 15y ago
  To be fair, it is only one of many compounds that are effective against specific traits of cancerous tumors. In this case, it is effective against tumors which are poorly vascularized. In most cases, one of the predominant features of tumor progression is the increase in vascularizing growth factors from cancer cells. Tumors which fail to start pumping out growth factors that encourage blood vessel growth often kill off the entire tumor due to lack of oxygen. Also, the apoptosis cascade can be hijacked in many locations. Even if you get the mitochondria to start releasing Cytochrome C (the main component that triggers the cascade), cancer cells can turn this pathway off anywhere downstream of CytC, such as turning off production of one of the various caspases. So, again, it comes down to cancer biology being incredibly complicated.
- refurb 15y ago
  Big pharma isn't ignoring it because of the patent issue, they are ignoring it because it doesn't work that well. They may not be able to get a "composition of matter" patent on it, but they could get a "use" patent on it. For a great example of a VERY common chemical that big pharma is developing, check out BG-12 from Biogen. It's dimethyl fumarate, something you can buy in ton quantities and most labs have jars of it. They are developing it for MS and it looks quite promising. http://www.drugs.com/clinical_trials/oral-bg-12-dimethyl-fumarate-significantly-reduced-multiple-sclerosis-ms-relapses-disability-12528.html http://www.drugs.com/clinical_trials/oral-bg-12-dimethyl-fum...
  - jimmyvanhalen 15y ago
    They don't know DCA doesn't work that well because they are not spending money on R&D. I agree they can get a use patent on DCA, as a matter of fact the researcher from University of Alberta already has a use patent on DCA as a cure for cancer. interesting info on BG-12. thanks.
    - refurb 15y ago
      Big drug companies are CONSTANTLY exploring new areas, trust me, they looked into DCA and found it wanting. I can't personally attest to the amount of R&D dollars spent by pharma on R&D, but it has been EXTENSIVELY studied, just checked out pubmed (gov't funded research). http://www.ncbi.nlm.nih.gov/pubmed?term=dichloroacetate http://www.ncbi.nlm.nih.gov/pubmed?term=dichloroacetate If DCA were an effective agent, they would have handed the U of A a handsome check for that use patent. They didn't, so what does that tell you?
jboggan 15y ago
A few years ago I did an analysis on common chromosomal deletions in ovarian cancers. I was hoping to find some sort of "required" genetic or metabolic structure retained by the various cell lines. Nada. It was just a big unrelated mess and deemed not interesting enough to write up by my advisor. I wish there was a Journal of Dishearteningly Negative Results.
- polyfractal 15y ago
  Depending on how "big" your negative result was, its possible to publish in journals similar to this: http://www.jnrbm.com/ http://www.jnrbm.com/
- tsotha 15y ago
  It makes sense to me. I once read a lung cell has to evade seven different anti-cancer mechanisms to become a malignant stem. If there are ten different ways to get around each defense, that would mean ten million different possible configurations of lung cancer, with all the therapeutic headaches that implies. Edit: And that's just for one cell type out of the myriad that compose a functioning lung.
joe_the_user 15y ago
Well, "Cancer isn't like a virus or pathogen that has evolved to avoid it our immune system..." until it start reproducing at a quick rate -then, as the article says "Tumor cells undergo evolution as they grow, so that the cells in them are genetically heterogeneous.". But another thing to think about is that science based medicine has so far been more or less powerless against degenerative diseases - in general. Our treatments for cancer, heart disease, arthritis and so-forth as basically ad-hoc as contrasted with our treatment of externally-caused disease. And this isn't surprising given that a degenerative disease is essentially a breakdown in engineering of the body and we essentially don't have a clue how to re-engineer or repair those processes (with many fine exceptions but they are exceptions). The genetic diversity that the author talks about in cancer is basically present fully functional human beings. The way that different people function is far more different than even the way two different cars work. When human any part of a human being breaks down, we can't in general produce a replacement. Sure, there are advances in understanding the processes involved but these are, again, ad-hoc so far.
- micro_cam 15y ago
  Evolution does occur in cancer cells in the sense of increased genetic variability which may lead to more aggressive/resistant cancer in a patient. However we won't see things like drug resistant staph infection because the genetics of the tumor don't spread beyond the individual. I also agree that our understanding of degenerative diseases is poor but I think that modern technology and methods will change this. Hopefully to the point were we can prompt the body to move the body from a diseased to a healthy state but that may be a ways out. However the genetic diversity in cancerous cells is not present in functioning human beings. Based on the analysis of genetic sequence data from tumor and blood samples from the same individuals it is clear that a large amount of mutation and structural variation occurs in cancer cells.

jimmyvanhalen 15y ago

Here's something interesting about a common chemical compound called Dichloroacetic acid (DCA). Big pharma is ignoring it since it can't be patented (because it's so common). Cancer cells change the way they metabolize oxygen in a way that promotes their survival. In laboratory studies of isolated cancer cells grown in tissue culture, DCA restores the original metabolism, and promotes their self-destruction. This has led to the use of DCA for treating cancer, by individuals experimenting with it themselves, by doctors administering it to patients as a non-approved drug, by scientists testing it in cancer tissue cultures in cell culture and in mice, and in human Phase II studies. DCA has improved certain biochemical parameters, but it has not demonstrated improved survival. Cancer cells generally express increased glycolysis, because they rely on anaerobic respiration that occurs in the cytosol (lactic acid fermentation) rather than oxidative phosphorylation in the mitochondria for energy (the Warburg effect), as a result of hypoxia that exists in tumors and malfunctioning mitochondria. [9] [10] Usually dangerously damaged cells kill themselves via apoptosis, a mechanism of self-destruction that involves mitochondria, but this mechanism fails in cancer cells. A phase I study published in January 2007 by researchers at the University of Alberta, who had tested DCA on human[11] cancer cells grown in mice, found that DCA restored mitochondrial function, thus restoring apoptosis, allowing cancer cells to self-destruct and shrink the tumor.[12] These results received extensive media attention, beginning with an article in New Scientist titled "Cheap, ‘safe’ drug kills most cancers".[11] Subsequently, the American Cancer Society and other medical organizations have received a large volume of public interest and questions regarding DCA.[13] Clinical trials in humans with cancer have not been conducted in the USA and are not yet final in Canada, emphasizing the need for caution in interpreting the preliminary results.[13][14] http://en.wikipedia.org/wiki/Dichloroacetic_acid http://en.wikipedia.org/wiki/Dichloroacetic_acid

polyfractal 15y ago
To be fair, it is only one of many compounds that are effective against specific traits of cancerous tumors. In this case, it is effective against tumors which are poorly vascularized. In most cases, one of the predominant features of tumor progression is the increase in vascularizing growth factors from cancer cells. Tumors which fail to start pumping out growth factors that encourage blood vessel growth often kill off the entire tumor due to lack of oxygen. Also, the apoptosis cascade can be hijacked in many locations. Even if you get the mitochondria to start releasing Cytochrome C (the main component that triggers the cascade), cancer cells can turn this pathway off anywhere downstream of CytC, such as turning off production of one of the various caspases. So, again, it comes down to cancer biology being incredibly complicated.
refurb 15y ago
Big pharma isn't ignoring it because of the patent issue, they are ignoring it because it doesn't work that well. They may not be able to get a "composition of matter" patent on it, but they could get a "use" patent on it. For a great example of a VERY common chemical that big pharma is developing, check out BG-12 from Biogen. It's dimethyl fumarate, something you can buy in ton quantities and most labs have jars of it. They are developing it for MS and it looks quite promising. http://www.drugs.com/clinical_trials/oral-bg-12-dimethyl-fumarate-significantly-reduced-multiple-sclerosis-ms-relapses-disability-12528.html http://www.drugs.com/clinical_trials/oral-bg-12-dimethyl-fum...
- jimmyvanhalen 15y ago
  They don't know DCA doesn't work that well because they are not spending money on R&D. I agree they can get a use patent on DCA, as a matter of fact the researcher from University of Alberta already has a use patent on DCA as a cure for cancer. interesting info on BG-12. thanks.
  - refurb 15y ago
    Big drug companies are CONSTANTLY exploring new areas, trust me, they looked into DCA and found it wanting. I can't personally attest to the amount of R&D dollars spent by pharma on R&D, but it has been EXTENSIVELY studied, just checked out pubmed (gov't funded research). http://www.ncbi.nlm.nih.gov/pubmed?term=dichloroacetate http://www.ncbi.nlm.nih.gov/pubmed?term=dichloroacetate If DCA were an effective agent, they would have handed the U of A a handsome check for that use patent. They didn't, so what does that tell you?

jboggan 15y ago

A few years ago I did an analysis on common chromosomal deletions in ovarian cancers. I was hoping to find some sort of "required" genetic or metabolic structure retained by the various cell lines. Nada. It was just a big unrelated mess and deemed not interesting enough to write up by my advisor. I wish there was a Journal of Dishearteningly Negative Results.

polyfractal 15y ago
Depending on how "big" your negative result was, its possible to publish in journals similar to this: http://www.jnrbm.com/ http://www.jnrbm.com/
tsotha 15y ago
It makes sense to me. I once read a lung cell has to evade seven different anti-cancer mechanisms to become a malignant stem. If there are ten different ways to get around each defense, that would mean ten million different possible configurations of lung cancer, with all the therapeutic headaches that implies. Edit: And that's just for one cell type out of the myriad that compose a functioning lung.

joe_the_user 15y ago

Well, "Cancer isn't like a virus or pathogen that has evolved to avoid it our immune system..." until it start reproducing at a quick rate -then, as the article says "Tumor cells undergo evolution as they grow, so that the cells in them are genetically heterogeneous.". But another thing to think about is that science based medicine has so far been more or less powerless against degenerative diseases - in general. Our treatments for cancer, heart disease, arthritis and so-forth as basically ad-hoc as contrasted with our treatment of externally-caused disease. And this isn't surprising given that a degenerative disease is essentially a breakdown in engineering of the body and we essentially don't have a clue how to re-engineer or repair those processes (with many fine exceptions but they are exceptions). The genetic diversity that the author talks about in cancer is basically present fully functional human beings. The way that different people function is far more different than even the way two different cars work. When human any part of a human being breaks down, we can't in general produce a replacement. Sure, there are advances in understanding the processes involved but these are, again, ad-hoc so far.

micro_cam 15y ago
Evolution does occur in cancer cells in the sense of increased genetic variability which may lead to more aggressive/resistant cancer in a patient. However we won't see things like drug resistant staph infection because the genetics of the tumor don't spread beyond the individual. I also agree that our understanding of degenerative diseases is poor but I think that modern technology and methods will change this. Hopefully to the point were we can prompt the body to move the body from a diseased to a healthy state but that may be a ways out. However the genetic diversity in cancerous cells is not present in functioning human beings. Based on the analysis of genetic sequence data from tumor and blood samples from the same individuals it is clear that a large amount of mutation and structural variation occurs in cancer cells.