One Of The Crowd

Over the course of this blog, I’ve tried to explain lots of stuff. I’ve covered subjects such as risk factors, what causes cancers to start growing, how different treatments work, what causes side effects and the decision-making processes that doctors use to plan a patient’s treatment.  And I hope I’ve managed to do it in a way that makes sense to readers without a scientific or medical background.

But the main aim of this blog has been to try and highlight the differences between the commonly held perceptions of cancer and the reality of this disease.  And if this blog has done its job, then you will have spotted the deliberate mistake in that sentence.  If you have, well done! Give yourself a Gold Star!  And if you didn’t spot it, the answer is at the end**, (although if you read through the rest of this post, rather than skipping straight to the end, it might give you a big clue!)

But I digress.  The aim of this post is to discuss another common misconception.  I’ve mentioned before that cancer patients often describe their tumour as a strange, alien “thing” that has invaded them.  Now, as I discussed in No Cure For Cancer…?, this is inaccurate.  The patient’s tumour isn’t an alien invasion, it is part of them.  But there is a second inaccuracy in this notion that a tumour is an alien “thing” that I want to cover in this post – and it is the idea that the tumour is a single “thing”.

It’s an easy mistake to make.  As a tumour forms, it grows as a single mass.  Even if the cancer is malignant and spreads, the patient ends up with two (or more) tumour masses, in separate locations.  And the most important word in the last paragraph is “mass”.  I used that word deliberately.  What is a “mass”? If you look up “mass” in the dictionary, you’ll find several definitions, but the one we are interested in is this one: “a large number of people or objects crowded together”.  This is what we mean by a tumour mass.  And this is the point I want to get across in this post.  A tumour is not one single, big thing.  Instead, it is made up of a huge collection of little things, namely cancer cells.

One of the Crowd 1

Look at the picture to the left. Image A is how most people visualise a tumour – as one big lump.  Now look at Image B. This one is closer to the truth.  A tumour is made up of lots and lots of little things – cells – all grouped together.  And, of course, it’s not just the tumour that is put together like this, your whole body is made the same way.  Every organ is made up of millions of cells, organised just right.

So, time for another of my Tortured Analogies (I know you love ’em!)  Think of your body like a huge crowd, say a crowd of football supporters.  Now, most of the time, in most grounds, the crowd obeys the rules.  The crowd goes through the right turnstiles.  The crowd uses the right stairwells.  The crowd goes to the correct sections of the ground.  The crowd sits in the right seats.  The crowd cheers in the right places, boos in the right places and sings the right songs.

But, of course, it is not the crowd that is doing all these things, because “the crowd” is not one single thing. Instead, it is made up of a huge number of individuals.  And it is the individual supporters who are doing all of these things.  Certainly, the individual members of the crowd talk to one another, but it is the individual who makes the decision to stick by the rules.

Now imagine that, in among the crowd, there is a hooligan element.  The hooligan element barges its way through the wrong turnstiles.  The hooligan element runs up the wrong stairwells, into the wrong sections of the ground.  The hooligan element rips up the seats.  The hooligan element sings offensive songs.  The hooligan element invades other sections and starts fighting. The hooligan element refuses to leave at the end….

But, again, it’s not the hooligan element that is doing all this, because “the hooligan element” isn’t one thing either.  It is also made up of individuals and it is the actions of individual eejits that ruin it for everybody.  And, granted, all of those individual numpties may behave in a similar way, but that doesn’t mean that they will always behave the same….

Much the same situation happens in cancer.  A tumour is not a single big lump, as in Image A above, it is a collection of individual cells, like in Image B.  And, like the hooligan crowd, all of those individual cancer cells may behave in a similar way, but that doesn’t mean that they all will, all the time.  This can help explain how a malignant tumour spreads. You may remember that I said, back in No Bootees, that a tumour turns malignant because it starts producing growth factors (Go! signals) that encourage bits to break off and start floating round the bloodstream.  But that is slightly wrong, because it assumes the tumour is a single thing, rather than a collection of individual cells.  And it is the behaviour of the individual cells that is important.

So, going back to our hooligan analogy, imagine a situation where all of them are ripping up seats.  But then, some of them decide it’d be a good idea to invade another section and start a riot in there.  Now, the ones who have this idea don’t bother checking with everybody else before they do it, they make the decision themselves, they just go.  Likewise, in the tumour, the Go! signals that encourage malignant cells to detach & spread won’t be produced by the entire tumour, but by a small number of individual cells, which then detach & float away.

But! It gets worse!  Going back to our hooligans, imagine that once some of them have invaded another area, they then turn back and shout out to the ones they left behind, urging them to do the same.  And some of them think, “Hey, that’s a good idea, I think I’ll do it too!”  And then this second bunch jump into other sections too.

One of the Crowd 2Well, recent research suggests that cancer cells can do the same.  So, while, initially, it will only be the tumour cells which produce the malignant Go! signals which detach and float away as in Image C on the left, they can communicate with the tumour cells left behind, by releasing factors which cause the non-invasive cells to turn invasive, as shown in Image D.

So, in future, keep an eye on your crowd.  And if you think some of them are misbehaving, do something about it ….. before your stadium gets trashed.

** Did you spot the deliberate mistake? I described cancer as “this disease”.  But, of course, as I’ve said before, cancer isn’t a single disease!  It is a large collection of different diseases!

Zomer, A., Maynard, C., Verweij, F., Kamermans, A., Schäfer, R., Beerling, E., Schiffelers, R., de Wit, E., Berenguer, J., Ellenbroek, S., Wurdinger, T., Pegtel, D., & van Rheenen, J. (2015). In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behavior Cell, 161 (5), 1046-1057 DOI: 10.1016/j.cell.2015.04.042

AG McCluskey (2015). One Of The Crowd Zongo’s Cancer Diaries


Marginal Gains

Marginal GainsThere are some common misconceptions about cancer. The first is one that I’ve spoken about before, namely the idea that cancer is a single disease. It isn’t. As I described back in No Cure For Cancer…?, the word “cancer” is an umbrella term used to describe a huge number of different diseases (over 200) that produce similar symptoms, namely uncontrolled cell growth.

But another big misconception is the one that I want to talk about here. It is the same one I mentioned back in Just One Cornetto, the one that the media continually try and punt – the idea that research into cancer is all about finding the “major breakthrough”, the “magic bullet”, the “wonder drug”….. This is nonsense. It isn’t how research works. And it isn’t how improvements in cancer treatment come about.  There have been no “major breakthroughs”. I doubt there ever will be. It’s the wrong way to think about it. Survival rates for cancer are improving, but not because of one huge change, but from numerous small improvements.

So, a better way to think of cancer research is to think of it as being a bit like the recent successes of UK cyclists in eg. the Olympics, Commonwealth games & Tour de France. UK cycling has gone through a real renaissance in recent years and UK cyclists have gone from being barely known about to household names: people such as Chris Hoy, Bradley Wiggins, Victoria Pendleton, Chris Froome… And when Dave Brailsford, the former performance director of British Cycling, was asked to explain the improved performances, he described the theory of Marginal Gains:

“The whole principle came from the idea that if you broke down everything you could think of that goes into riding a bike, and then improved …. [each thing] … by 1%, you will get a significant increase when you put them all together”.

For a cyclist, what this means is making little changes.  Lots of little changes.  They’ll change what they eat, they’ll change how they sit on a bike, they’ll change how they train….. But that is not all.  The cyclist won’t just change his or her fitness and training regime or diet, they’ll change everything.  They will also change they way they sit in a chair, or lie in bed to try and conserve energy and ensure they are properly rested.  They will even take the same pillows, mattresses and quilts when they travel.   They will change what they wear.  They will even change how they wash their hands, to reduce the chances of infection.  And when all of these changes are put together, it results in a huge improvement in overall performance.

cs_surv_trendsAnd the same is true for cancer statistics.  Take a look at the figure on the left.  This shows how the survival rates for common cancers have improved over the last 40 years***.  Now, some survival rates are a lot better than others, obviously, but that is to be expected given that we are talking about a huge variety of different diseases.  But the main thing is that the arrows all point to the right.  Across the board, survival is improving.

Now, the point is, these improvements have not been caused by giant leaps forward – by major breakthroughs – but by lots of smaller things added together.  In some cases it is improvements in diagnosis, meaning that the cancers are being caught earlier.  Also, as I mentioned in Bullseye!, improvements in scanning technology has improved the targeting of radiotherapy, leading to more precise treatments and improved outcomes.

And, obviously, new chemotherapy drugs have been developed.  But the changes in outcome from the new drugs that have come through in the last 40 years have not come from huge, major changes.  Instead, they have made relatively small improvements.  Now, when I say that, it is a bit simplistic.  So, rather than saying specific changes make small improvements, it would be better to say that specific changes improve the outcome for a small number of patients.

Imagine that a new chemotherapy drug is being developed. Now different drugs will have different ways of working, but let’s say that this particular drug targets a growth signal.  Now, before the drug enters the clinic, the research team, who think that this new drug may be effective in Lung Cancer, take a look at a range of patient tumour biopsy material, to see if the specific growth signal – the target  of the new drug – is there.  And they discover that the signal is only present in 10% of Lung Cancer patients.

Now, in one sense, this could be considered a huge disappointment.  After all, it means that 90% of patients will not benefit from the new drug.  But the research team won’t focus on who won’t benefit, they focus on who will – ie the 10%.  So, in Science-speak, they will say that there is a specific Patient Cohort, representing 10% of total Lung Cancer patients, where the new treatment could be very effective.  And when the research team check through biopsies of patients with other types of cancer, they find that their drug’s target is also found in 8% of Breast Cancers, 2% of Prostate Cancers, 4% of Colorectal Cancer…..

So, we have small numbers of patients, with different diseases, who could potentially benefit from the new treatment.  Now, if you look at the individual numbers, you might think, “Only effective in 2% of Prostate Cancer?  That’s rubbish!”, but the point is, all of these little numbers add up…..

And THAT is what causes improvements in cancer treatment.  Ignore what the Media says – it’s not about the “major breakthrough”, it is about Marginal Gains – lots and lots of little changes, that add up to overall increases in survival rates.

*** You can find more information on Survival trends over time for common cancers on the CRUK website, HERE, or in the article listed below:

Quaresma, M., Coleman, M., & Rachet, B. (2015). 40-year trends in an index of survival for all cancers combined and survival adjusted for age and sex for each cancer in England and Wales, 1971–2011: a population-based study The Lancet, 385 (9974), 1206-1218 DOI: 10.1016/S0140-6736(14)61396-9

AG McCluskey (2015). Marginal Gains Zongo’s Cancer Diaries


Trumpity Trump!Interesting story on the BBC today.  Apparently, elephants are less likely to get cancer than humans!  This story is based on the results of this study, which examined cancer rates in a variety of species.  They found that, while in humans the overall risk of contracting cancer is 11-25%, in elephants it is only 5%.  Now, this could be considered surprising, considering what I have previously told you about the common risk factors associated with cancer.

Back in Chinese Whispers, I mentioned that cancer is regarded as an age-related condition – the older you live, the bigger the risk of getting the disease.  Also, in No Bootees, I explained that cancer is caused by an imbalance in growth signals and, in my last post, I spoke about the observation that tall people are more likely to get cancer than short people, possibly because they make more growth signals.  Now if you take all this together, you would expect that the older and bigger something is, the bigger the risk of cancer.  But elephants are much, much bigger than us, and they also have pretty long life spans.  So why is their risk of cancer so much lower than ours……?

Now, obviously, elephants live (primarily) in the wild, so it could be that the lower incidence of cancer is simply due to the fact that they are dying of other things – poaching, disease, poor nutrition etc. – but, even after the research team had put controls in place to account for these possibilities, the risk of cancer was still much lower in elephants.

To try and find out why, the researchers had a look at the elephant genome and compared it to the human version, to look for differences in genes that are known to be related to cancer.  And they found something interesting.  While the human genome contains one single copy of a certain gene called p53, the elephant genome contains up to twenty copies! Now, why is this important?

Back in No Bootees, I described how your body is constantly replacing old, dead cells, by modulating the levels of growth factors to make new ones.  So, your cells will produce factors that encourage cells to grow and divide (Go! signals) and then switches the system off after the dead cells have been replaced, by making factors that prevent growth and division (Stop! signals).  Well. p53, the gene that is multiplied in elephants, is a Stop! signal.  More than that, it is THE Stop! signal!  There are genes which can induce cancer (called “oncogenes”) and there are genes which can prevent cancer forming (called “anti-oncogenes”).  And the most important anti-oncogene we know of is p53.

p53 has many functions, and all of them help to prevent cancer.  The three most important roles it plays are in DNA Repair, Cell Cycle Arrest and Apoptosis.

One of the reasons why cancers can begin is gene mutation, which is where the DNA that makes up your genes gets altered.  If your DNA becomes damaged, then this can be dangerous, because if it isn’t repaired properly, you will end up with mistakes in the DNA, which can change how the gene works.  If this happens inside a gene which controls cell growth, the upshot can be increased Go! signals and this can lead to cancer.  So, the cell will attempt to repair any DNA damage which occurs, and p53 is one of the signals that helps to activate the repair process.  And the first thing it does is shout “STOP!”  This makes the cells freeze where they are and therefore stops the cells dividing in two.  The process of cell division is called the Cell Cycle, so stopping this process is Cell Cycle Arrest.  So, there we have two of the main functions of p53.  It stops the cells dividing and helps initiate DNA repair, both of which can help prevent the normal cell from changing into a cancer cell.

And then we come to p53’s other main function.  Apoptosis.

We scientists love our high-falutin’ words, and “Apoptosis” is a doozy, isn’t it?  The word comes from the ancient Greek words for “separate “ and “fall” and the word “apoptosis” was originally used to describe the way that leaves die and fall off of trees in Autumn.  And that gives an idea of what the word means in a cellular biology setting, that cells will decide to die, when the time is right.  So, another (less fancy) way of saying Apoptosis is “Programmed Cell Death”.  What happens is, if a cell detects an imbalance in the growth signals – too many Go! or not enough Stop! – the cell will try to correct the imbalance.  But….what if the cell can’t fix it?  What happens then?  Well, as a last resort, the cell will initiate a Self Destruct mechanism, to stop itself turning into a cancer cell.  And so, the dodgy cell kills itself and the potential crisis (ie. cancer) is prevented.  Apoptosis is the name given to the Self Destruct mechanism.  And p53, the gene that is multiplied in elephants, is a control switch for this process.

This is why the  researchers say that elephants have reduced risk of cancer.  The higher levels of p53 mean that you would expect their cells to have increased activation of DNA damage repair processes, increased arrest of cell growth in response to DNA damage and increased levels of Apoptosis.  And, indeed, the research team found all of these in elephant cells.

Now for the big question: How does all of this help us?  Answer:  It doesn’t.


While the fact that elephants have increased levels of p53 wasn’t known before, p53 itself has been known about for a looooong time.  There has been a helluva lot of research into the function of p53 – research which is ongoing.  So, this isn’t new.  But the big problem is this: everything I’ve said about p53 describes what it does in normal cells to prevent cancer.  But, obviously, cancers exist.  So, how can that happen, if p53 is so good at stopping it?  The answer is both obvious and deeply depressing.  In the majority of cases of cancer, p53 is missing.  It is either mutated (ie. altered so it doesn’t work), or it is switched off.  In one sense, that is how cancers happen in the first place.  If a cell is damaged, or has an imbalance of Go! signals, then p53 activates and stops it becoming cancerous.  But if, inside these cells, p53 is also damaged, then these protective mechanisms don’t work and there is nothing to stop the cancer beginning.  And that is what all of the research into p53 has been trying to do – to try and either replace the missing/faulty p53, or to try and “kick-start” the p53 response in cancer cells, in order to try and turn the cancer cell back into a normal cell.

So, while the fact that elephants have more p53 than us is interesting, it isn’t going to help us stop human cancers anytime soon.  And it may not be the whole reason why elephants get cancer less than us anyway. As Prof Mel Greaves from the Institute of Cancer Research in London explains, there are plenty of other reasons why the cancer risk in humans is so high:

“You’ve never seen an elephant smoke!”

Abegglen, L., Caulin, A., Chan, A., Lee, K., Robinson, R., Campbell, M., Kiso, W., Schmitt, D., Waddell, P., Bhaskara, S., Jensen, S., Maley, C., & Schiffman, J. (2015). Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans JAMA DOI: 10.1001/jama.2015.13134

AG McCluskey (2015). Trumpity-Trump! Zongo’s Cancer Diaries

Tough luck, Stretch!

Tough luck stretchWe’ve all heard that tall people have it better than short people.  Tall people tend to earn more money and are perceived to be more intelligent.  And, if you are a man, the taller you are, the more desirable you are.  And, at least in my experience, they definitely find it easier to get served at the bar.

But now we have a fightback from us Shorties!  It was reported today that tall people are more likely to contract cancer than short people.  Hah!  In your face, lanky!  Serves you right for always sitting in front of me at the cinema!

Now, the first thing to say is, don’t panic if you are above average height.  The correlation between height and risk of cancer has been known about for years.  This present study is just the latest to find the correlation.  And, as I previously discussed in Just One Cornetto, correlation is not causation.  And we are not talking about direct causes here, we are talking about risk factors, which I discussed back in Chinese Whispers.  So just because increased height correlates with an increased risk of cancer, it doesn’t mean that increased height causes cancer.  It may (may!) increase the risk, but probably not by a very significant amount.

In one sense, it isn’t that surprising.  As I mentioned in No Bootees, cancer is caused by an imbalance in growth signals inside cells.  And, obviously, a person’s height is due to the number of these signals they produce as they grow.  So, if they are making more signals, they will get taller, but also have an increased chance of an imbalance.  But, compared to some other well known risk factors, the chances of this happening are pretty small.  Generally speaking, the main risk factors are still the ones we all know; Smoking (which is estimated to cause almost a fifth of all cancer-related deaths), Obesity (which is thought to cause about 1 in 20 cancers) and diet (which is implicated in about 10% of cases).  There are also genetic risk factors which can increase the risks massively (eg. it is estimated that 65% of women who carry BRCA mutations will develop Breast Cancer).

Compared to these numbers, the risks of developing cancer from being on the lanky side are pretty small.  While the study that has been talked about today has not been published yet, previous studies have shown that height-associated risks were significantly lower than other factors, such as smoking and obesity.

If you want to reduce your risks of cancer, then stop smoking and watch what you eat.  And if you have a family history of certain types of disease, investigate the possibility of there being a genetic trait that could be involved.  But don’t worry about your height, it aint that big a deal.

So don’t panic, Stretch!  And don’t try and take a hacksaw to your kneecaps – It wouldn’t work anyway!

AG McCluskey (2015). Tough Luck, Stretch Zongo’s Cancer Diaries