4 ms·

The best approach to cancer therapy is to focus on the commonalities shared by all cancer. At the moment that means lengthening of telomeres. Every cancer does

The best approach to cancer therapy is to focus on the commonalities shared by all cancer. At the moment that means lengthening of telomeres. Every cancer does it. If you can suppress telomerase and ALT (alternative lengthening of telomeres), or if you can reliably identify the biochemistry of cells abusing telomerase and ALT, then you can kill any cancer. E.g. a universal cancer vaccine based on this approach: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471666/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471666/ E.g. disable part of the mechanism by which telomerase lengthens telomeres: http://www.eurekalert.org/pub_releases/2015-05/cndi-csa051115.php http://www.eurekalert.org/pub_releases/2015-05/cndi-csa05111... People such as the SENS folk have been advocating this approach for more than a decade, but the research community is slow in adopting it. The vast majority of cancer research continues to be a matter of doing very expensive things that only work for one tiny subtype of cancer. If we're doing expensive things, then they should be efficient expensive things.

nonbel 11y ago
>"The best approach to cancer therapy is to focus on the commonalities shared by all cancer. At the moment that means lengthening of telomeres." Do you have a source for this? Has someone actually measured telomere elongation in a bunch of different tumor biopsies and reported detection in >90%?
- JoeAltmaier 11y ago
  I think that's backward. Its shortened teleomeres that are linked to cell malfunction? Elongation is the supposed cure. Or is there a syndrome where cancerous cells keep lengthening theirs? Ah I see the article mentions this. But years ago it was understood that cancerous cells originally happened because of damage from short teleomeres? That end-of-life cells would divide badly and malfunction, sometimes by reproducing endlessly. So its a matter of timing? Young people want to keep their teleomeres long; but if you get cancerous cells then you want to clip them all. Sadly, that means end-of-life for the rest of your body. But no more cancer.
  - adenadel 11y ago
    The simple notion is that you want long telomeres to resist aging. Cancer cells "want" long telomeres to maintain their "cellular immortality", their ability to divide indefinitely. From Wikipedia: "Telomeres are critical for maintaining genomic integrity and studies show that telomere dysfunction or shortening is commonly acquired during the process of tumor development. Short telomeres can lead to genomic instability, chromosome loss and the formation of non-reciprocal translocations; and telomeres in tumor cells and their precursor lesions are significantly shorter than surrounding normal tissue."[0] "Cancer cells require a mechanism to maintain their telomeric DNA in order to continue dividing indefinitely (immortalization). A mechanism for telomere elongation or maintenance is one of the key steps in cellular immortalization and can be used as a diagnostic marker in the clinic. Telomerase, the enzyme complex responsible for elongating telomeres through the addition of telomere repeats to the ends of chromosomes, is activated in approximately 80% of tumors."[0] It's not as simple as long vs short. 0. https://en.wikipedia.org/wiki/Telomere#Cancer https://en.wikipedia.org/wiki/Telomere#Cancer
    - nonbel 11y ago
      Interesting. Wikipedia makes that 80% claim, citing: Aschacher; Wolf; Enzmann; Kienzl (2015). "ALINE-1 induces hTERT and ensures telomere maintenance in tumour cell lines". Oncogene. doi:10.1038/onc.2015.65. Aschacher et al write: "In about 80% of tumour cells, telomere maintenance is controlled by telomerase (TA), a reverse transcriptase, which adds DNA repeats onto chromosomal ends."12, 22, 23, 24, 25 I checked all five references and none had anything about this 80% of tumors number. It appears to be made up.
- reasonattlm 11y ago
  https://www.google.com/#q=cancer+hayflick+limit https://www.google.com/#q=cancer+hayflick+limit
  - nonbel 11y ago
    Thanks, but nothing on the first page links to actual data of the type I am looking for. It would be more efficient if someone who already knows the data source could link directly to it rather than others independently rifling through search results and citation trees to find it.
    - reasonattlm 11y ago
      Read the Wikipedia entry on the Hayflick limit and follow its references. You are actually better off as a layperson doing the thing you are objecting you - looking through materials - as it will enable you to pick the context, which you won't if you head straight for the one line summary point. http://hmg.oxfordjournals.org/content/10/7/677.full http://hmg.oxfordjournals.org/content/10/7/677.full "Telomerase activity has been found in almost all human tumors but not in adjacent normal cells."
      - nonbel 11y ago
        Thanks. They cite Kim et al (1994) and Shay and Bacchetti (1997). Table 2 of Kim et al shows up to 38% telomerase activity in normal tissue (ie head and neck) and in only 25% of breast cancers. Similarly Shay and Bacchetti reported telomerase activity in many normal tissue samples (eg table 2 GI tract normal was 25% table 9 normal epidermis was 44%). Also, Shay and Bacchetti write: "With very few exceptions, tumor cells were assayed by the PCR-based TRAP protocol... negative samples from the few studies that used the less sensitive assay without PCR amplification of telomerase products, have been disregarded". These papers are pretty old, so I thought it would be interesting to find out what has been learned about the TRAP protocol in the time since. Today, we know those methods lead to false positives: "The original TRAP method has several drawbacks. Initially, the CX oligonucleotide, which complementarily overlaps with TS for several bp, is used in the amplification of PCR products. It results in the dimerization of primers and products that emerge due to the interaction between primers. Even when using the optimal ACX primer with the noncomplementary TS end, a background signal may emerge during the analysis of concentrated extracts from tumor tissues [14]. An additional problem is encountered when using reverse primers which completely correspond to telomeric repeats. The primers are not annealed at the matrix edges during PCR (as a result of periodicity in telomeres), and hence false signals emerge." http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347595/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347595/ It would be interesting to see more recent data on this.
berntb 11y ago
Didn't the SENS people say that the real trick is to have two or even three different treatments for any given cancer -- then use them in parallel? It would be hard to evolve around multiple attacks at the same time.
nonbel 11y ago
For example, see table 1 here (they find ~90% of tumors are aneuploid): http://www.ncbi.nlm.nih.gov/pubmed/17046232 http://www.ncbi.nlm.nih.gov/pubmed/17046232 Is there similar data available regarding telomeres?
astazangasta 11y ago
There are lots of things that every cancer must do. Read one of Bob Weinberg's "hallmarks of cancer" papers for an overview. Telomeres are just one thing. They must also activate growth signalling, evade the immune system, promote vascularization, repress tumor suppression mechanisms or otherwise avoid apoptosis or senescence, etc. All of these are valid targets for therapy, and most of them have been tried.
- nonbel 11y ago
  Weinberg is apparently now of the opinion that cancer research is so full of shit it is not even worth trying a replication project. Not kidding: >"Critics have dismissed the cancer-study endeavour as time-consuming, out-of-touch with the realities of basic science and unlikely to produce interpretable results. “It’s a naÏveté that by simply embracing this ethic, which sounds eminently reasonable, that one can clean out the Augean stables of science,” says Robert Weinberg, a cancer biologist at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts." http://www.nature.com/news/cancer-reproducibility-project-scales-back-ambitions-1.18938 http://www.nature.com/news/cancer-reproducibility-project-sc... Probably due to all the retractions he had to deal with out of his lab recently: http://retractionwatch.com/2015/07/06/cancer-research-retraction-is-fifth-for-robert-weinberg-fourth-for-his-former-student/ http://retractionwatch.com/2015/07/06/cancer-research-retrac... I wonder how much he still believes what he wrote in 2000.

nonbel 11y ago

>"The best approach to cancer therapy is to focus on the commonalities shared by all cancer. At the moment that means lengthening of telomeres." Do you have a source for this? Has someone actually measured telomere elongation in a bunch of different tumor biopsies and reported detection in >90%?

JoeAltmaier 11y ago
I think that's backward. Its shortened teleomeres that are linked to cell malfunction? Elongation is the supposed cure. Or is there a syndrome where cancerous cells keep lengthening theirs? Ah I see the article mentions this. But years ago it was understood that cancerous cells originally happened because of damage from short teleomeres? That end-of-life cells would divide badly and malfunction, sometimes by reproducing endlessly. So its a matter of timing? Young people want to keep their teleomeres long; but if you get cancerous cells then you want to clip them all. Sadly, that means end-of-life for the rest of your body. But no more cancer.
- adenadel 11y ago
  The simple notion is that you want long telomeres to resist aging. Cancer cells "want" long telomeres to maintain their "cellular immortality", their ability to divide indefinitely. From Wikipedia: "Telomeres are critical for maintaining genomic integrity and studies show that telomere dysfunction or shortening is commonly acquired during the process of tumor development. Short telomeres can lead to genomic instability, chromosome loss and the formation of non-reciprocal translocations; and telomeres in tumor cells and their precursor lesions are significantly shorter than surrounding normal tissue."[0] "Cancer cells require a mechanism to maintain their telomeric DNA in order to continue dividing indefinitely (immortalization). A mechanism for telomere elongation or maintenance is one of the key steps in cellular immortalization and can be used as a diagnostic marker in the clinic. Telomerase, the enzyme complex responsible for elongating telomeres through the addition of telomere repeats to the ends of chromosomes, is activated in approximately 80% of tumors."[0] It's not as simple as long vs short. 0. https://en.wikipedia.org/wiki/Telomere#Cancer https://en.wikipedia.org/wiki/Telomere#Cancer
  - nonbel 11y ago
    Interesting. Wikipedia makes that 80% claim, citing: Aschacher; Wolf; Enzmann; Kienzl (2015). "ALINE-1 induces hTERT and ensures telomere maintenance in tumour cell lines". Oncogene. doi:10.1038/onc.2015.65. Aschacher et al write: "In about 80% of tumour cells, telomere maintenance is controlled by telomerase (TA), a reverse transcriptase, which adds DNA repeats onto chromosomal ends."12, 22, 23, 24, 25 I checked all five references and none had anything about this 80% of tumors number. It appears to be made up.
reasonattlm 11y ago
https://www.google.com/#q=cancer+hayflick+limit https://www.google.com/#q=cancer+hayflick+limit
- nonbel 11y ago
  Thanks, but nothing on the first page links to actual data of the type I am looking for. It would be more efficient if someone who already knows the data source could link directly to it rather than others independently rifling through search results and citation trees to find it.
  - reasonattlm 11y ago
    Read the Wikipedia entry on the Hayflick limit and follow its references. You are actually better off as a layperson doing the thing you are objecting you - looking through materials - as it will enable you to pick the context, which you won't if you head straight for the one line summary point. http://hmg.oxfordjournals.org/content/10/7/677.full http://hmg.oxfordjournals.org/content/10/7/677.full "Telomerase activity has been found in almost all human tumors but not in adjacent normal cells."
    - nonbel 11y ago
      Thanks. They cite Kim et al (1994) and Shay and Bacchetti (1997). Table 2 of Kim et al shows up to 38% telomerase activity in normal tissue (ie head and neck) and in only 25% of breast cancers. Similarly Shay and Bacchetti reported telomerase activity in many normal tissue samples (eg table 2 GI tract normal was 25% table 9 normal epidermis was 44%). Also, Shay and Bacchetti write: "With very few exceptions, tumor cells were assayed by the PCR-based TRAP protocol... negative samples from the few studies that used the less sensitive assay without PCR amplification of telomerase products, have been disregarded". These papers are pretty old, so I thought it would be interesting to find out what has been learned about the TRAP protocol in the time since. Today, we know those methods lead to false positives: "The original TRAP method has several drawbacks. Initially, the CX oligonucleotide, which complementarily overlaps with TS for several bp, is used in the amplification of PCR products. It results in the dimerization of primers and products that emerge due to the interaction between primers. Even when using the optimal ACX primer with the noncomplementary TS end, a background signal may emerge during the analysis of concentrated extracts from tumor tissues [14]. An additional problem is encountered when using reverse primers which completely correspond to telomeric repeats. The primers are not annealed at the matrix edges during PCR (as a result of periodicity in telomeres), and hence false signals emerge." http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347595/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3347595/ It would be interesting to see more recent data on this.

berntb 11y ago

Didn't the SENS people say that the real trick is to have two or even three different treatments for any given cancer -- then use them in parallel? It would be hard to evolve around multiple attacks at the same time.

nonbel 11y ago

For example, see table 1 here (they find ~90% of tumors are aneuploid): http://www.ncbi.nlm.nih.gov/pubmed/17046232 http://www.ncbi.nlm.nih.gov/pubmed/17046232 Is there similar data available regarding telomeres?

astazangasta 11y ago

There are lots of things that every cancer must do. Read one of Bob Weinberg's "hallmarks of cancer" papers for an overview. Telomeres are just one thing. They must also activate growth signalling, evade the immune system, promote vascularization, repress tumor suppression mechanisms or otherwise avoid apoptosis or senescence, etc. All of these are valid targets for therapy, and most of them have been tried.

nonbel 11y ago
Weinberg is apparently now of the opinion that cancer research is so full of shit it is not even worth trying a replication project. Not kidding: >"Critics have dismissed the cancer-study endeavour as time-consuming, out-of-touch with the realities of basic science and unlikely to produce interpretable results. “It’s a naÏveté that by simply embracing this ethic, which sounds eminently reasonable, that one can clean out the Augean stables of science,” says Robert Weinberg, a cancer biologist at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts." http://www.nature.com/news/cancer-reproducibility-project-scales-back-ambitions-1.18938 http://www.nature.com/news/cancer-reproducibility-project-sc... Probably due to all the retractions he had to deal with out of his lab recently: http://retractionwatch.com/2015/07/06/cancer-research-retraction-is-fifth-for-robert-weinberg-fourth-for-his-former-student/ http://retractionwatch.com/2015/07/06/cancer-research-retrac... I wonder how much he still believes what he wrote in 2000.