Cancer is even more complicated than we thought

There's some really interesting—and rather disturbing—research coming out of the UK on the nature of cancer cells and why advanced-stage cancers are so difficult to treat.

Scientists have long known that the same type of cancer can play out in very different ways, from a genetic perspective, in one patient compared to another. But this new research shows that, even within the same patient—even within the same tumor—different samples of cancer cells have more genetic differences than they have similarities.

That's a very big deal. It means that cancer cells aren't just cells that grow uncontrollably. They also mutate. Which means that they evolve. That fact has serious implications for cancer treatment. Just like bacteria can evolve to become resistant to antibiotics, cancer cells can evolve resistance to the treatments we throw at them. At Not Exactly Rocket Science, Ed Yong explains how this discovery fits into the bigger picture of why curing cancer is so damned difficult:

For a start, cancer isn’t a single disease, so we can dispense with the idea of a single “cure”. There are over 200 different types, each with their own individual quirks. Even for a single type – say, breast cancer – there can be many different sub-types that demand different treatments. Even within a single subtype, one patient’s tumour can be very different from another’s. They could both have very different sets of mutated genes, which can affect their prognosis and which drugs they should take.

And now we know that's true within a tumor, as well. At the Cancer Research UK blog (where Ed used to work), Henry Scowcroft has a nice summary of how this one discovery explains three perplexing problems we've long had with cancer cells:

Firstly, cancer is very difficult to cure after it has spread. This is despite years of progress in chemotherapy and radiotherapy, two techniques that can offer respite to people with advanced cancer.

Secondly, most advanced cancers eventually become resistant to every type of drug used to treat them – both ‘traditional’ chemo and these newer agents. This is quite extraordinary: tumours can work out how to cope with chemicals that they’ve never ‘seen’ before – a biological superpower far beyond that of infectious diseases. Just consider how it’s taken ‘multidrug resistant’ bacteria like MRSA decades to evolve. Yet cancers can do this in a matter of months or even weeks. How?

And finally, researchers haven’t yet managed to develop tests to predict how a patient’s disease will progress, nor monitor their progress (a field called ‘biomarker’ research) – this is despite years of research, and a lot of tantalising pilot studies. Sometimes researchers detect a promising ‘signal’ by looking at samples from a handful of patients, only for this to disappear in larger numbers of people.

Read Ed Yong's full story on this research.

Read Henry Snowcroft's full story on this research.


  1. Gosh cancer pisses me off – why is it that the most horrendous, painful, malevolent thing gets all of these ridiculous nearly supernatural abilities? All of that just goes towards hurting the host as fast as possible rather than anything productive, anywhere, ever. It’s like the troll of biology.

    1. Hear hear. And why is it so hard to start some kind of international mobilization and actually succeed in reducing the numbers… we can get together and mobilize when it comes to killing people, but not when it comes to saving their lives. Funny that.

      1. I wouldn’t be so negative. There’s a huge amount of international work and cooperation in the cancer research community, and the survival rates are continuously climbing – though of course not as fast as we’d prefer.

        1. I find it quite hard to be positive cause this is a bit too close to home right now. Also, deaths might decrease but the figures when it comes to number of people afflicted are increasing rapidly. I find very little to be cheerful about.

          1. How about this: Cancers are non-transmittable, so every new case inherits nothing from those before. That means that any treatment found will work, on average, equally well for every future patient. Compared to how bacteria and viruses keep evolving defences against everything we come up with, that’s very useful: Every small step is a permanent improvement.

      2. Agree with you… no one like or even dream about having such disease… it’s horrible thing even just to think about it, i pray for someone who fight with it…  

  2. My wife has a breast cancer op scheduled for next wednesday. I really wish I hadn’t read this. Make mine a large unicorn.

    1. Sorry to hear about your wife.  Sometimes, cancer is all gotten during surgery, and at other times by subsequent radiation and/or chemo.  You never know, that’s why early detection is so important.  As better genetic tests are developed, I bet those tests will tell you if the cancer can be beaten back or not.  Except for longtime cigarette smokers, we have little cancer in my family (other genetic issues, but not cancer).  But in my husband’s family – both parents and 3 of 4 grandparents all died from cancer.

    2. Hang in there.  My best wishes for your wife’s speedy and FULL recovery.

      We go at cancer guns a-blazin’ because we have to get the entire tumor on the first go.  If cancer cells are left on the margins, those secondary regrowths are much harder to stamp out than a centralized mass.  That means these early treatments are extremely harsh.  But it is all for a good cause, and I am hoping for the best for you.

  3. As long as all they can do is point to symptoms and not a cause, cancer is a symptom. Symptoms don’t “mutate”. Maybe they need to go back and re-examine their assumptions.

    1. That doesn’t make any sense. Cancer cells are living things like pathogens, only derived from the host. There are a number of carcinogens known to create them, and like most cells they are quite capable of creating more of themselves. What “cause” are you looking for?

    2. Disclaimer: I am not a medical researcher (my background is in electrical engineering), but the following is my understanding (someone please correct me if I am wrong).

      Cancerous cells are those that have undergone some sort of genetic mutation, resulting in their “misbehaviour.” So, what causes genetic mutations? Well, lots of things do (everything classified as a carcinogen, among other things), including background radiation that we are exposed to everyday. But, our cells are able to correct many genetic mutations, and many mutations result in cell death (are not carcinogenic), so it becomes largely a statistical game. Which mutations will result in cancer and what are the chances that our bodies cannot correct for it before it gets out of control? Randomness plays a large role in the process.

      So, good luck finding “the” cause.

      1. You’re right that at any given time, our bodies contain some pre-cancers that are taken care of before they progress.   But randomness is not entirely to blame.  We often are feeding these pre-cancers exposures continuously, even upon identification of the cancer, continuing to feed it an exposure.  Or exposures.  

        There are many theories on this, that I’m not gonna touch with a 10 foot pole.  But it’s possible that the exposures that we feed the precancers (things we eat, drink, breathe, ARE genetically, & come into contact with) outpace the body’s ability to repair.  It might not be so random.  

        1. Just to clarify, by random, I mean in the stochastic sense (i.e., non-deterministic, probabilistic), not in the “that’s a totally random thing we can’t control” sense. Certainly, if we increase our exposure to carcinogens, we will increase the probability that we will get cancer. But, it does not guarantee that we will get cancer and the factors that affect the stochastic model appear to be very complex (why are there some people that smoke like a chimney and live to be 92?).

  4. As someone who has been in treatment for cancer for nine years now, and endured seven lines of chemo along with surgeries and radiation, I feel I have earned the right to say, “Duh-doy!”

  5. And some cancers are contagious. To the best of my knowledge none in humans as of yet, but there’s at least one known type in dogs. Imagine if one of the human ones makes that same jump.

    Added creepyness – technically, every dog that has that cancer has pieces of the first dog that had it growing in them, as it’s not a contagious virus that causes cancer, but the cancer itself that spreads from host to host.

  6. It is this complexity that has become visible that also holds the seed of real cures: cures targeted to specific metabolic pathways that we can see from genetic data.  It’s called “synthetic lethality”.

    Unfortunately when each of those 200 subtypes have 50 driving mutations, every cancer becomes a rare disease, and our system of clinical trials fails. 

    Not to mention that genetic data remains apart from clinical practice, despite the enormous international project to sequence cancers and link human genomes to diseases.

    1. That link between the genetic data and clinical practice certainly is happening.  At the company where I work, we have developed a test based on the gene expression profile for normal thyroid tissue (I wrote the software which runs the test), and we’ve been running it for more than a year now.  I just read a story in the news yesterday about a woman from Fall River, MA, who took our test, not knowing whether her thyroid nodule was cancerous (it wasn’t, to her obvious relief), and it does make you realize that this kind of technology can improve the quality of people’s lives so much.

      There will be many more of these types of tests coming to market as next generation sequencing becomes more accessible.  We’re currently using custom microarrays from Affymetrix, mainly because they’re approved for clinical use, but more and more sequencing technologies are also getting FDA approval for diagnostic use, and it’s a technology we’re obviously very interested in. 

      But your point about subtype variance is well taken; we’re fortunate in that we are only looking at deviations from the normal thyroid tissue gene expression profile, so, by definition, anything outside of that is inherently suspicious. We do call certain cancer subtypes, though, both primary and metastatic, but it is clear that it would be very useful clinically for us to be able to discriminate more precisely between them.

  7. Cancer is an interesting beast. It’s not enough of a problem to kill off the species, so it hasn’t evolved itself out of existence. Childhood cancer is still rather rare. Most cancers happen in older people that would have been dead of various other diseases before modern health care and public health came along. It’s considered by some researchers to be an inevitable byproduct of life itself.

    I sometimes wonder whether it wouldn’t make more sense to just let some of the more virulent cancers kill people, rather than subject them to the often-barbaric and often-ineffective and always-expensive treatments that our medical establishment has come up with. It’s a tough call. And before you call me insensitive, I’ve gone through 2+ years of cancer treatment with my own son, and I’ve had friends die of cancer after years of treatment, so I know both sides of the story.

    1. Inasmuch as we have a social structure designed to provide health care to individuals using shared resources, I think it’s always fair to question whether extreme measures are justified, at least at public expense. My own preference is to err on the side of “too much” rather than “too little”, but the line does need to be drawn somewhere. We can’t afford unbounded expenditures for any single patient.

      Beyond that, sure…each patient should be allowed the choice of how to proceed. If they do not want to experience the hardships involved in cancer treatments, surely it would be cruel for us as a society to force that on them. But as far as I know, that’s generally not a problem, is it?

      Are there mentally and legally competent cancer patients being treated against their will?

  8. Biology PhD student here.

    This is kind of old news.  It has been appreciated for a long time that one of the major hallmarks, and probably one of the major causes, of cancer is “genomic instability.”   That means that cancer cells are constantly mutating, gaining or losing whole chromosomes,the large, continuous strands of DNA, of which our genome has a total of 46 usually.  This is especially true in more malignant forms of cancer.  What happens is that the very machinery that our cells use to recognize and fix problems with our genome becomes damaged, leading to greater and greater degrees of damage to the genome each time the cell divides.  This is also a common target for chemotherapy.  Our cells actually have multiple maintenance pathways for the genome and usually cancers only involve the loss of one of these pathways.  A common strategy, especially for breast cancer which often involves these problems with genome repair (the very unfortunately copyrighted BRCA breast cancer mutation is in a genome repair pathway), involves blocking the other repair pathways as well in an attempt to make rapidly dividing, and therefore mutating, cells so damaged that they cannot survive.  The real sad news is the evolving capabilities of cancer cells has shown us examples of cancer cells actually fixing their original repair defects in order to survive the chemotherapy.

    In the coming era of genomic medicine, that is treatment defined by each individuals genome, the best that we can hope for is that knowledge of these susceptibilities to problems with genome repair will allow for early diagnoses of cancer and treatment before large, heterogeneous, evolving tumors can even form.

  9. Can’t help thinking that if we crack these, we will figure out a great deal more about how genetics work, and how cells function. And since it’s cancer, we have a lot of motivation and funds to do so. Cancer sucks — guess our medical research will just have to be that much more awesome.

    (I recently lost my grandma, not to cancer, but to damage done by cancer treatments. But she was the kind of person who would be glad to know if data collected from her case – along with so many others – went toward saving lives down the road.)

  10. “Cancer” is a symptom. Being able to treat the symptom is a fine thing, but to prevent it we need to get to the causes — plural — which share that symptom.

    1. If you’re going to repost the same nonsensical talking point, the least you can do is stop being cryptic and tell us all which woo-woo theory it is that you’re pushing. 

  11. Watch Run from the Cure on Youtube. Cannabis Oil has put people into remission. In 1938 a Noble Prize went to a researcher who showed that Cancer cannot live in a low alkaline environment. My neighbor here in Washington is regularly putting people into remission with Kengan water and raw vegetables in 30 days after their Doctors sent them home to die.

  12. we can dispense with the idea of a single “cure”

    Only in the short term, until we get at the root of the problem. (Disclaimer: transhumanist here.) There is a single origin of cancer, which is genetic malfunction of cells. If we developed something that either kept cell’s programming on track or could universally identify and destroy cells that went awry, all types of cancer could be indeed cured.

    In fact, the body almost does this. Microcancers are constantly being identified and eliminated by your immune system. Some of the most promising treatments for  cancer on the horizon now involve helping the immune system do its thing.

  13. Cancer researcher, information theorist, and transhumanist here. Yes, these all go happily together, though I have no idea how they managed to get /me/ in on this.

    The biggest problem, in my opinion, isn’t the notion that cancer is exactly one class of illness with an isolated set of cures. Rather, it’s that scientists, at least in my experience, are very bad at handling the complexities of the combinatorial explosion. I’m not talking about the “big data” problem here — the community at large has the capabilities necessary to process and analyze petabytes of data, end-to-end. 

    Rather, they’re getting hung up on the more fundamental things: defining data standards, making all of these data available to a wider audience, and understanding and disseminating the right algorithms to approach and understand what’s there. 

    Most of the day-to-day research is still embarrassingly manual. The field is having difficulties making meaningful progress because it’s having trouble attracting the right people — techheads, genome hackers, algorithmists, mathematicians, and information theorists like me — primarily for social and political reasons. The pay isn’t as good as your workaday programmer or other technical position, biologists need large amounts of convincing to adopt algorithms that are correct but non-intuitive, and the governments backing these initiatives are very bad at publishing the data necessary to get any interesting work done.

    Well, screw all that noise. Here’s how you can get involved and help, right now: 

    The data is there. And what we most need is people to look at it, help us classify it, and write us better tools to make medical research more intelligible, more understandable, and easier for us to do good science. 

    So get in there, play with it, and most importantly: have fun, while helping us make this world a much better place for everyone.

    (Full disclosure: I work at a non-profit medical research institute in Seattle, Washington, and receive federal funding under The Cancer Genome Atlas (TCGA) project. Obviously, it’s in my professional best interest for you all to make my job easier, but please: help us help you help us all. :) )

  14. Actually it is simple.

    Every second in your body there are cancer cells which are being removed by the immune system. Therefore cancer is a failure of internal defence mechanisms. What causes mutation? Toxins, radiation. What fries immune system? Long-term stress.

    The funny part is that chemotherapy and radiotherapy cause cancer themselves.

    Source: works of Bruce Lipton, Gabor Mate.

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