Why havent we cured cancer yeeeeeeeeet?

Posted by ERV on February 6, 2012
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Last time I talked about why treating cancer is so hard:

Why havent we cured cancer yeeeeeet?

Briefly, scientists did complete genome sequencing of seven individuals prostate tumors, and things were all kinds of jacked up. Not only were all seven tumors different, but one tumor had over 200 chromosomal rearrangements. Like taking your genome and shuffling it like a deck of cards.

As if that kind of complexity isnt bad enough…

Another group of scientists sequenced the genomes of acute myeloid leukaemia patients pre- and post-treatments:

Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing

Turns out some tumors react to chemotherapy the same way bacteria respond to antibiotics and HIV-1 responds to antiretrovirals:

But the HIV-1 monster does not want. HIV-1 operates as a ‘quasispecies’, that is, a large population of genetically distinct, yet related organisms. It turns out that no matter how many lazrs scientists pointed at the HIV-1 quasispecies… they could not kill all of them! Just by chance, the quasispecies contains variants that are resistant to every lazr. Luckily, these variants are less fit than a wild-type virus– ‘resistance’ comes at a fitness cost. HAART keeps viral loads low because its harder for the drug resistant viruses still alive to reproduce.

But the HIV-1 monster DO NOT WANT! Slowly, but surely, these less-fit resistant variants start accumulating secondary compensatory mutations, which create viruses that are resistant to teh lazrs, but ALSO are extraordinarily fit. This is when HAART fails, and the patient needs to switch drugs.

Because of the genomic diversity of the population of tumor/bacteria/virus, when you apply the treatment, there is a small sub-population that is resistant to the treatment. That small sub-population replicates (+ the associated mutations) selecting for increases in replication capacity in the presence of the drug.

Carl Zimmers description (en pointe, as always):

The cancer cells grew in number, and as they did, they accumulated a lot of mutations, some of which are listed in the figure next to the star. All of these mutations, one after the other, took over the entire population of cells-a signature of natural selection. When the woman went to her doctor, however, the cancer had diversified into a number of different lineage, each carrying additional, distinctive mutations. Over half of the cells belonged to a lineage marked here in purple, known as cluster 2. Cluster 3, marked in yellow, was made up cells with a separate set mutations. And from within Cluster 3 emerged yet another lineage-Cluster 4, marked in orange. The dots in each circle show the sets of mutations that accumulated in each cluster.

The chemotherapy knocked down all the clusters of cancer cells to such low numbers that doctors couldn’t find them any more. But they were still there. And when exposed to chemotherapy drugs, the most successful cluster was not the one that had been most successful back when the cancer was diagnosed. It was the relatively rare Cluster 4. Apparently, it had mutations that made it better able to withstand the chemotherapy drugs. Some its descendants later picked up new mutations, which enabled them to reproduce quickly and take over the cancer population, as they resisted new chemotherapy drugs as well.

These are just long ways of saying: Evolution–>drug resistant tumors.

Well shit.

Another reason why treating cancer is so damn hard.

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  2. #2 sasqwatch
    February 6, 2012

    It’s just God’s way of telling us how much He loves us, and that he wants us to come home sooner rather than later.

  3. #3 Tum
    February 7, 2012

    At least the mutations that the individual cancer collects are not spread from person to person, and do not live on once the person dies. Drug resistant pathogens on the other hand give me the creeps. If one develops cancer, one has at least a chance if it is detected early enough. Get a resistant bug? Tough luck, mate.

    Damn you Orgel! Damn your second rule! Damn you Darwin! Damn your Evilution! *Shakes angrily fist*

    If you look at 100 (or more) cancers (let’s say prostate cancer), how similar are the mutations and rearrangements between different patients? Is there a “common theme”?

  4. #4 Tum
    February 7, 2012

    Never mind, after reading your older blog-post I came to the conclusion: what a stupid question of mine. And if there was a “common theme” found, we would have heard about it by now.

    While we are at it: There are many different forms of cancer and there are many things that either cause cancer or a risk factor for cancer. Radiation as a cause of cancer? That I can understand. Toxins? Not sure, but one could come up with mechanisms I guess. Retroviruses? ASFAIK the integration into the DNA messes up the genome of the cell, no wonder if a cell can get out of control. But how do other viruses cause cancer?

  5. #5 techskeptic
    February 7, 2012

    @Tum #3

    True, but it is possible. Cancer spreads in tasmanian devils, even though it is non-viral.

    http://en.wikipedia.org/wiki/Devil_facial_tumour_disease

  6. #6 EvilYeti
    February 7, 2012

    Cancer, or malignant neoplasms, isn’t really a disease. It’s more a symptom than anything.

    And that damage is almost entirely a product of the modern era.

    see: http://www.dailymail.co.uk/sciencetech/article-1320507/Cancer-purely-man-say-scientists-finding-trace-disease-Egyptian-mummies.html

  7. #7 mo (one of Abbies's elk)
    February 8, 2012

    No.

    http://www.nature.com/nrc/journal/v11/n1/full/nrc2914-c2.html

  8. #8 sasqwatch
    February 8, 2012

    Consider the source, EvilYeti.

  9. #9 Randy
    February 8, 2012

    I am in total agreement with TUM. Drug resistant pathogens, while providing me with a a fair amount of work in the hospital lab, are the looming specter of doom for me. Seriously, when heavy hitters like Gent and Vanc don’t do the trick we are seriously up the creek. At least with the big “C” you aren’t spreading it around, unless you are Madame Curie.

  10. #10 Aj
    February 8, 2012

    Cancer, or malignant neoplasms, isn’t really a disease. It’s more a symptom than anything.
    And that damage is almost entirely a product of the modern era.
    see: http://www.dailymail.co.uk/sciencetech/article-1320507/Cancer-purely-man-say-scientists-finding-trace-disease-Egyptian-mummies.html

    They looked for cancer in the Egyptian mummies and couldn’t find it, ergo no cancer 6 thousand years ago?

    In a further shocking discovery they found that people in ancient times had straw where today we rely on our internal organs to keep us alive.

    In conclusion if you remove your lungs, heart, brain and giblets, you to can be cancer free

    (In next week’s Mail on Sunday – “Replacing your organs with straw may be the latest fashion, but will it give you cancer?”)

  11. #11 EvilYeti
    February 8, 2012

    Sasqwatch, I did. The original article was published in Nature.

    http://www.nature.com/nrc/journal/v10/n10/abs/nrc2914.html

    I post the pop-culture stuff as its most appropriate for the reading level of this audience. Additionally, not all of you have subscriptions to Nature.

    Hey mo, checked your reference. It says this:

    “Based on this evidence the authors proposed that cancer was rare in antiquity. However, this conclusion might need further verification as they neglected the literature and evidence from China.”

    That’s a pretty soft statement given your rather emphatic “no”.

    You’ll also notice my soft language, in that I said “almost entirely”. Meaning “not entirely”.

  12. #12 Bryan
    February 8, 2012

    EvilYeti,

    Having read the article, I’m unimpressed. The crux of their claim is:
    a) signs of cancers are rare (but not non-existent) in preserved specimens (mummies) and historical accounts, and
    b) Although their life expectancies are shorter than ours, they do live long enough to see some sign.

    The problem with that arguments are many, but even taking their best-case-example of a life expectancy of 50 years, their supposition falls flat. Looking at modern rates, cancers which occur by age 50 account for 5%, perhaps 10%, of all diagnosed cancers:
    http://info.cancerresearchuk.org/cancerstats/incidence/age/

    Looking at the adult life expectancy for Egyptians (~40yrs) – whom are the best source of mummies where these cancers can be detected – gets you into the range of about 1% of all diagnosed cancers.

    Meaning, unless the authors can convincingly show that incidence of cancers in mummies is <1% of the rate observed today (taking into account missing organs, etc), their hypothesis doesn’t have a leg to stand on.

    Plus there is the data from China, which shows that the ancient Chinese, at least, were well aware of cancer.

    Overall, incidence is up today, but that can largely be explained by our increased lifespans. Incidence of certain specific cancers has changed dramatically – prior to the 1940′s, stomach cancer was common. The advent of wide-spread refrigeration has made it one of the rarer cancers today. In contrast, lung cancers are far more common due to tobacco use. But I’m unaware of any data convincingly showing that overall age-adjusted incidence has increased, and the aritlce you posted is far too flawed and limited to conclude anything.

  13. #13 Bryan
    February 8, 2012

    part of my last post disappeared. Where it said “Meaning, unless the authors can convincingly show that incidence of cancers in mummies is ”

    it should have continued to say “[incidence of cancers in mummies is] less than 1% that observed today, they don’t have a leg to stand on.

  14. #14 EvilYeti
    February 8, 2012

    Bryan,

    There is a tremendous amount of data linking environmental pollution to cancer. I’m not making some kind of huge leap in logic here.

    I’m also from New Jersey, which is somewhat notorious for its pollution. New Jersey also has a higher incidence of cancer than the national average. Call me crazy, but I don’t think that’s a coincidence.

  15. #15 harold
    February 8, 2012

    Both untreated and treated/relapsing cancer are examples of mutation/natural selection, at the cellular level. However, the abnormal cells that are transiently selected for eventually go extinct, by destroying the host, unless the cancer is successfully treated.

    And that damage is almost entirely a product of the modern era.

    see: http://www.dailymail.co.uk/sciencetech/article-1320507/Cancer-purely-man-say-scientists-finding-trace-disease-Egyptian-mummies.html

    Incorrect.

    First of all this claim is specifically about ancient Egypt. Ancient and medieval sources discuss cancer directly. Hippocrates, Galen, etc.

    Furthermore, the claim is probably incorrect about ancient Egypt. Mummies are a small sample, mainly of cadavers of relatively young people (life expectancy was much shorter, but there may also have been a tendency not to mummify the elderly). You might not expect to find much cancer, for sampling reasons alone. Furthermore, most internal organs were removed in Egyptian mummification. And certain types of cancer, such as leukemia, might not be detectable in a mummy. The work is valuable and interesting but the claim that there was no cancer in ancient Egypt cannot remotely be supported.

    There is a tremendous amount of data linking environmental pollution to cancer. I’m not making some kind of huge leap in logic here.

    Yes, you are making a huge leap in logic.

    You are jumping from the completely correct idea that pollutants and other environmental factors can markedly raise the risk of some forms of cancer – which no reasonable person would deny – to the wrong idea that modern pollution is the only possible risk factor for cancer, and that cancer did not exist in pre-modern times. The existence of cancer in ancient and medieval times is well documented.

  16. #16 Bryaan
    February 8, 2012

    EvilYeti,

    I never denied that effects like pollution don’t affect cancer – I even pointed out one example (lung cancer). However, it is a huge stretch to extend an increase in one type of cancer, driven by modern environmental factors, to the incidence rate of all cancers. We know some are up; but others are down. For net incidence, we have no clear data. There are historical accounts of cancer, and evidence from some recovered remain, of cancer in earlier times. But not enough to make any conclusions about incidence. The task is even more herculean, as cancers tend to form late in life – far later in life than most people lived in historical times. There simply isn’t enough data to conclude one way or another.

    Bryan

  17. #17 EvilYeti
    February 10, 2012

    It’s painfully obvious none of you have read the original paper so I don’t see a point in continuing this discussion.

    And here’s a hint, ignorance and critical thinking are two drastically different things.

  18. #18 Witch
    February 26, 2012

    Back to why haven’t we cured cancer yet?
    Because with chemo”therapy”, we’ve been led up the garden path.
    See the editorial in The Australian Prescriber, “The emperor’s new clothes – can chemotherapy survive?” According to the original research, the contribution of chemotherapy to the survival of cancer patients is less than 3%, and that’s being generous.

    Source:
    Australian Prescriber Editorial: The emperor’s new clothes – can chemotherapy survive?
    Available at: http://www.australianprescriber.com/magazine/29/1/2/3/

    The research referred to:

    Morgan G, Ward R, Barton M. The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. Clin Oncol 2004;16:549-60
    Abstract available at – http://www.ncbi.nlm.nih.gov/pubmed/15630849

  19. #19 EvilYeti
    February 26, 2012

    Whenever someone talks about “curing” cancer it makes my OCD crawl.

    Cancer is the result of genetic damage. Much like a burn is the result of excess heat applied to flesh.

    Neither can be cured. The best you can do is focus on prevention and treatment.

    Btw, still think cancer isn’t a ‘modern’ problem?

    http://en.wikipedia.org/wiki/Cancer#Causes

    Cancers are primarily an environmental disease with 90-95% of cases attributed to environmental factors and 5-10% due to genetics.[1] Environmental, as used by cancer researchers, means any cause that is not genetic, not merely pollution[citation needed]. Common environmental factors that contribute to cancer death include tobacco (25-30%), diet and obesity (30-35%), infections (15-20%), radiation (both ionizing and non-ionizing, up to 10%), stress, lack of physical activity, and environmental pollutants.[1]