The Angry Silence

Angry SilenceMy last post discussed the findings outlined in the recent report from MacMillan Cancer Support, Cancer: Then and Now.  Previously, I concentrated on the improvements in cancer survival rates over the last 40 years and described how this was due to improvements in diagnosis and treatment options.

But in this post I’m going to talk about another thing that the MacMillan report highlighted as having changed dramatically since the 1970’s.  Something which also has a major impact on the quality of life for cancer patients and can also, as we are now beginning to understand, contribute to increased chances of survival.

Talking.

30-40 years ago, cancer was a taboo subject.  People didn’t talk about it.  In those days, cancer was seen as a Bogey man, a terrifying spectre that shouldn’t be mentioned in case it tempted fate.  A diagnosis of cancer was seen as an automatic death sentence, so the very mention of the word struck terror in the hearts and minds of even the strongest and most courageous.

So someone diagnosed with cancer 30 years ago would suddenly find the world a dark, terrifying place.  Not only were survival rates poor, but they would often find themselves isolated, unable to speak to anyone about their fears.  One patient is quoted as saying, “In the 1980s there was no one to help or advise.  I felt very alone and frightened, and thought I was going to die.”

But, also, not only did cancer patients find it hard to talk to friends and loved ones, there was also very little information available to them from medical professionals.  This is backed up by the medical staff involved, as one oncology nurse who worked in the 1980’s explains, “Cancer was hush, hush.  Our job was to explain what cancer was in the kindliest way as there were no story lines in television soaps, no magazine features about people with cancer to relate to.”

So, up until the ‘80’s, being a cancer patient must have been utterly terrifying.  They had no information.  They wouldn’t have gotten any from medics or nurses.  They wouldn’t be able to share their experiences to anyone outside of their immediate families or close friends – and that’s assuming their friends & families would want to talk about it at all.

And even if they did survive, there was nothing, nothing in the way of aftercare or psychological support to help them cope and process the extremely traumatic experiences they had been through.

Think about that for a minute.  A diagnosis of cancer is incredibly stressful. Undergoing treatment is incredibly stressful.  And even surviving is incredibly stressful.  Imagine doing all of that with virtually no support, no help, no one to turn to.

No one to talk to.

But that has changed in the last 30 years. Oh, don’t get me wrong, a cancer diagnosis is still a stressful experience.  And treatment and recovery is no picnic either.  But one big difference (other than the improvements in diagnosis and planning I’ve already spoken about) is that cancer is not a dirty word anymore.  There’s not anywhere near the same level of secrecy and taboo associated with cancer diagnosis as there was back then, so current cancer patients won’t be as isolated as they would have been in the past.

The information available for patients nowadays is vast.  MacMillan themselves offer advice and support and CRUK’s webpage is a huge resource.  Also, the number of personal testimonies out there, in the form of books, movies, blogs etc. mean that there are plenty of reassuring voices.  And all of this can make the experience for patients less stressful.  Not stress-free, you understand, but infinitely better than it used to be.

And this can be important for another reason.  One which is remarkable, but still not well understood.  It can help improve survival.

Studies through the years have found that a patient’s psychological state can influence the success or failure of their treatment.  Generally speaking, patients who experienced depression, distress or a lack of social support had poorer outcomes.  In contrast, those patients who had large, supportive social networks had a lower relative risk of cancer mortality of between 12-25%.

But what could be causing this?  Well, according to this review, stress can induce the production of mood-altering hormones, which can affect normal bodily functions such as the immune system, inflammation and blood-flow.  And these alterations in bodily function can make the environment more favourable for tumour growth and spread.

So, if anyone reading this has cancer or if you know someone who does, make sure you keep talking.  Not only will the patient feel better, it might actually help make them better too.
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Lutgendorf, S., & Andersen, B. (2015). Biobehavioral approaches to cancer progression and survival: Mechanisms and interventions. American Psychologist, 70 (2), 186-197 DOI: 10.1037/a0035730

MacMillan Cancer Support (2016). Cancer: Then and Now. Diagnosis, treatment and aftercare from 1970–2016 MacMillan Cancer Support

ResearchBlogging.org
AG McCluskey (2016). The Angry Silence Zongo’s Cancer Diaries

Live Long & Prosper!

A bit of good news today.

Macmillan Cancer Support have released a report, Cancer: Then and Now, which shows that people diagnosed with cancer are twice as likely to survive for at least a decade they were in the early 1970s.

Cancer incidence rates UK 1979-2013Now this is a great thing to see.  Quite often, I’ve heard people complaining about the fact that cancer incidence rates have risen since the 1970s.  And it’s true, more people are diagnosed with cancer nowadays, as you can see in this graph from CRUK.  For both men and women, while the lines may wobble a bit, the overall trend is an increase in cancer incidence.  On average, the incidence rate in 1979 was 450 per 100,000.  By 2013, this had risen to 600 per 100,000.  Or, to express it as the relative risk so popular in the media, cancer incidence rose by 33.3% in that timeframe.  Now this can seem down-heartening.  Depressing, even.  And Scary.  But what does this increase actually mean?

I’ve heard complaints that this increase is down to our lifestyles.  E numbers in food….GMOs….poor diets…..pollution…..you name it.  And, in one sense, these people are right.  In a sense, increased cancer incidence is down to our lifestyles.  Just not in the way that they imagine.

UK Life expectancy 1980-2012As I’ve mentioned before – waaaaay back in Chinese Whispers – cancer is, generally, a disease of aging.  The longer you live, the bigger the probability that you’ll get cancer.  And that’s the point.  Yes, it’s true that cancer incidence has increased since the 1970s, but so has life expectancy.  This figure from UK National Statistics, and it covers, more or less, the same timeframe as the cancer incidence figure above.  Now, what you can see right away is that life expectancy is also increasing on average, from 71 & 77 for men and women respectively in 1980, to 78.7 & 82.6 in 2010-12.  And this equates to a rise of approx 11% for men and 7% for women.

So we are living longer.  And as cancer is more likely the longer you live, cancer rates would be expected to rise.  “But!” I hear you cry, “Surely cancer incidence is rising faster than life expectancy!”  Why would that be??”

Well, for a start, this is a logical fallacy.  There’s no direct connection between the two sets of statistics, so there’s no reason to expect that they will go up or go down by exactly the same amount.  And people do die from other things, so this will lower life expectancy.

But it is also down to one of the factors highlighted in the MacMillan report.  We are getting better at diagnosing cancer – and in early diagnosis.  So, 40 years ago, people might have cancer for a long time before diagnosis.  Some may even have died from undiagnosed diseases.  But improvements in scanning technology and in the development of tests for cancer-specific markers mean that this is less likely.  So we can spot these things earlier.  And the earlier a disease is found, the more treatable it is.

Marginal Gains 2I’ve shown this figure from CRUK before – and I’m more than happy to show it again!  This one shows how the survival rates for the commonly found cancers in the UK have changed from the early 70s until 2010.  And, as you can see, all the arrows are pointing to the right.  Survival is increasing across the board.  So, yes, cancer incidence rates are increasing.  But detection & survival rates are increasing too.

Better chemotherapy treatments are available.  Cancer patients are fast-tracked to ensure their treatment starts earlier.  The improvements in scanning technology which allow better diagnoses also give surgeons a better view of tumours – where they are, how big they are, whether they’ve spread.  And that makes successful surgery more likely and also increases the potential for other treatments such as radiotherapy.

Does this mean everything is Okay-Dokay-Fine?  No, of course not.  There’s still a lot to do.  But, in a time where it seems as if everything’s going down the crapper (Hi there, Brexit!  Yo, President Trump!), it’s nice to have a wee bit of good news for a change.  And if you are suffering from cancer, or know someone who is, then that’s what you’ll get today.  This is the (ahem) “best” time there’s ever been to be a cancer patient.  You’re chances of surviving, of living a long & happy life are better now that they’ve ever, EVER been.  Might not seem like much, but that tiny sliver of light can mean a helluva lot, if all you see is darkness.

So have a good day, folks.  Live Long & Prosper.

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MacMillan Cancer Support (2016). Cancer: Then and Now. Diagnosis, treatment and aftercare from 1970–2016 MacMillan Cancer Support

ResearchBlogging.org
AG McCluskey (2016). Life Long & Prosper! Zongo’s Cancer Diaries

Computer Says No

Anti-cancer therapy and Autoimmune disease:  Part II

Computer Says NoSo, in my last post I gave a brief description of Autimmune conditions.  Now, I’m going to describe the ways that research into cancer treatments is impacting on these diseases.

There was a big splash in the Media last Friday about a potential new treatment for certain forms of Multiple Sclerosis (MS).  And the basis of that treatment?  Chemotherapy.  Yes, that’s right, cancer chemotherapy.  MS patients are being treated with high doses of chemotherapy drugs to try and alleviate their symptoms.  But why would you do this??  And how can it work?

I’ve spoken before about the common side-effects of cancer therapies such as chemotherapy and radiotherapy.  Back in Bullseye! I described how these treatments can damage the patients’ immune systems.  And this can be very bad for the patient, obviously.  But the thing is, something which is bad in one setting can actually be good in another.

Listen to me!  I sound like one of those self-help books.  Turn that frown upside down! Accentuate the positive, eliminate the negative!  Take a sad soooong and make it better…..  But this, in essence, is the basis of the new treatment for MS that is being investigated.

So MS, like other Autoimmune diseases, is caused by an out-of-control immune reaction.  So, what could you do to you fix it?  How could you get the immune response back under control?  Well, conventional treatments have tried to suppress the immune response in these patients.  This has only had limited success, unfortunately.  This led some researchers to consider something more drastic. They decided to treat the immune system like a computer.

Picture the scene:  You’re on your PC, and it stops working.  What do you do?  Easy.  Chances are, you switch it off, then switch it back on again.  And you hope that this’ll fix the problem.  But what if it doesn’t work?  What if you find that the program is corrupted?  Well, you can erase the corrupted version from your hard-disk and then re-install a clean version.  And this, essentially, is the concept behind the new treatment for MS.

In cancer patients, there is an extreme form of treatment that is sometimes used which involves very high doses of chemotherapy or radiotherapy.  Now, this may, or may not, destroy the patient’s tumour.  Obviously, it’s hoped that it’ll be the former!  But one thing it definitely will do, as a side-effect, is destroy the patient’s immune system.  This is obviously not great, so in order to mitigate these unwanted side-effects, clinicians will repair the damage to the patient’s immune response by restoring the immune system after treatment.  They do this using a technique called haemopoietic stem cell transplantation.

The haemopoietic stem cells live in your bone marrow and are the cells which give rise to all the different types of immune system cells.  These are destroyed by the high dose therapy and this is what damages the patient’s immune system irreparably.  So, knowing this is going to happen, clinicians remove some of the haemopoietic stem cells from the patient and store them before the high dose treatment is administered.  After the treatment has finished, the clinicians can then put the patient’s haemopoietic stem cells back into their body, where they will grow and divide, and recreate the patient’s immune system.

So, that is what happens in cancer.  But how does this apply to MS? Well, clinicians realised that what was a negative in a cancer setting – the destruction of & replacement of the immune system – could be a positive in the case of Autoimmune diseases.  Autoimmune conditions are caused by aberrant immune responses, and high-dose chemotherapy or radiotherapy destroys the immune response.

So clinicians theorised that, like a computer, the use of high dose anti-cancer therapies, coupled with haemopoietic stem cell recovery & transplantation might erase the corrupted version of the patients’ immune systems and replace them with a rebooted, correctly functioning version.

So, a trial was conducted where haemopoietic stem cells were isolated from 24 MS patients.  The 24 patients were then dosed with very high doses of chemotherapy drugs, which destroyed their immune systems.  Then, the haemopoietic stem cells were put back.

Now.  Sounds easy, yeah?  Well…..no.  This treatment is not straightforward.  Far from it.  It is incredibly tricky.  And, it is incredibly risky. Chemotherapy drugs can have very, VERY nasty side-effects – and not just against the immune system.  Indeed, one of the patients actually died during the course of this treatment, and all of the others suffered from a variety of pretty serious side-effects.  So, not a walk in the park, by any means.

But, in the 23 patients who survived the treatment, the early results seem to be very promising.  Their rebooted immune systems appear, so far, to be functioning normally, with no evidence of MS-related activity.  Some of them have reported that their symptoms gave stabilised.  Others have actually seen an improvement in their conditions, recovering their mobility and quality of life.

So, all good, so far.  And, as well as MS, similar studies are ongoing in patients with other Autoimmune conditions, such as Scleroderma.  Now it’s still early days.  There’s no way of knowing how long the rebooted immune systems in these patients will maintain their normal function.  Hopefully, their immune systems will remain normal for a very, very long time.  But, it’s possible that their rebooted immunity might contain the same flaws as the original, so that the Autoimmune conditions re-emerge.  But even if this is the case, when could this happen?  Dunno.  There’s no way to tell yet.

Also, there is no way of knowing what other long-term effects will be caused by the high dose treatments.  This approach is basically using a sledge-hammer to crack a nut – it hits the immune system, certainly, but it hits a lot of other things too.  Studies of cancer survivors have shown that these high dose treatments can damage the digestive system, liver, kidneys, cardiovascular system and many others.  And a lot of this damage may not become apparent for many years after the treatment has ended.  So, it’s likely that similar side-effects will also be observed in the follow-up studies of the MS & Scleroderma patients taking part in these trials.  So, a lot (and I mean, a LOT) of extra study will be needed to work out the long-term health risks of this approach.

And remember, this is just the early stages of this type of approach.  If it can be shown to have real long-term benefits, then it will help drive research into finding more immune-specific treatments that can avoid potential off target side-effects.  But that still needs to be determined.  All we can say is that for now, for right now, we have a therapy which has the potential to be a major breakthrough in the treatment of MS, Scleroderma and other Autoimmune diseases.

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Dr Harold L Atkins, MDcorrespondenceemail, Marjorie Bowman, MScN, David Allan, MD, Grizel Anstee, MD, Prof Douglas L Arnold, MD, Prof Amit Bar-Or, MD, Isabelle Bence-Bruckler, MD, Paul Birch, MLT, Prof Christopher Bredeson, MD, Jacqueline Chen, PhD, Prof (2016). Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial The Lancet : http://dx.doi.org/10.1016/S0140-6736(16)30169-6

Craciunescu, O., Steffey, B., Kelsey, C., Larrier, N., Paarz-Largay, C., Prosnitz, R., Chao, N., Chute, J., Gasparetto, C., Horwitz, M., Long, G., Rizzieri, D., & Sullivan, K. (2011). Renal Shielding and Dosimetry for Patients With Severe Systemic Sclerosis Receiving Immunoablation With Total Body Irradiation in the Scleroderma: Cyclophosphamide or Transplantation Trial International Journal of Radiation Oncology*Biology*Physics, 79 (4), 1248-1255 DOI: 10.1016/j.ijrobp.2010.05.036

ResearchBlogging.org

AG McCluskey (2016). Computer Says No Zongo’s Cancer Diaries

Collateral Damage

Anti-cancer therapy and Autoimmune disease:  Part I

Collateral DamageBit of a detour in this post, as I’m going to be talking about Autoimmune diseases.  There is a cancer connection though, which is the current trials into the use of anti-cancer therapy to treat these Autoimmune conditions.  But, in order to explain how this works, I need to explain what Autoimmune diseases are.  So, that will be the subject of this post.  In the next one I’ll go on to discuss the current attempts to treat these diseases with chemotherapy and radiotherapy.

So.  Here we go.  Autoimmune disease 101:

Autoimmune diseases are caused by errors in the patient’s immune system.  Now, your immune system is there to do a very specific, very important job.  It’s there to protect you against infection.  The cells of your immune system circulate through your body, looking for anything that doesn’t belong.  If they find anything, they attack & destroy it.  This is how you fight off viruses, bacteria, fungal infections, etc.

So that’s what the immune system does.  It wanders about, looking for a fight.  But why doesn’t it start a fight with your own cells?  Well, as I described back in No Cure For Cancer…? every cell in your body has a protein on the outside called MHC, which acts like an “identity card” for the immune system.  So, normally, the immune system will ignore any cell which has the correct “identity card”, which is why it’s so hard to activate an immune response to cancer cells.

But, unfortunately, in some people this system breaks down.  Their immune systems stop recognising the “identity card” on some of their cells, which leads to them being incorrectly labelled as foreign invaders.  It’s a bit like the reports we’ve all heard from Iraq & Afghanistan, where innocent civilians are incorrectly identified as Enemy Combatants and blown to bits.  “Collateral Damage” is the oddly benign euphemism for this.  And the same thing happens in an Autoimmune disease.  So, the immune system goes on the offensive and starts to attack the supposed “foreign invaders”.

Different cell types come under attack in different Autoimmune diseases. In Rheumatoid Arthritis it is the joints. In Scleroderma it is the connective tissue that surrounds your blood vessels & major organs. And in MS it is a specialised cell type called oligodendrocytes.  I’m now going to describe the situation in MS, but similar events occur in Rheumatoid Arthritis, Scleroderma and other Autoimmine conditions.

So, in MS, the cells that comes under attack are the oligodendrocytes, which are part of your Central Nervous System (CNS).  The CNS is how information moves from your brain to your body and vice versa.  So, if you feel hot or cold, hurt yourself or feel hungry etc, then the information travels up the CNS to the brain.  If you decide to move your arms & legs, pick your nose or whatever, then your brain sends the appropriate signals to your body via the CNS.  Now, the signals work like electrical currents travelling through your nerves, in much the same way as the electricity running through the wires that power appliances like your TV, tablet, PC, etc.  In these appliances, the electrical wires  are covered in plastic insulation to prevent short circuits, which can damage the appliance, possibly irreparably.

And, in exactly the same way, your nerves are also covered in insulation to prevent “short circuits” in your CNS.  This biological insulator is called Myelin, and it is made by the oligodendrocytes.  So, in people with MS, the out-of-control immune response attacks & destroys the oligodendrocytes.  This means that their bodies can no longer make the insulating Myelin which protects the nerves in their CNS.  Therefore, their nerves become exposed, and this results in “short circuits” in their CNS.  And this is what causes the symptoms of MS.

In other Autoimmune conditions, the same thing happens.  In Rheumatoid arthritis, the painful swelling and deformation in the patients’ joints is caused by damage to the cartilage and bone.  In Scleroderma, damage to the connective tissue under the skin and around internal organs and blood vessels, leads to hard, painful swelling on the skin, circulatory problems and organ failure.  But in each case, like MS, the real issue in the aberrant, out-of-control immune response.

Right!  Now you have a (very!) brief description of Autoimmune diseases in general and MS in particular.  In the next post, I’ll go on to describe the potential of anti-cancer therapies for treating these conditions.

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Bell, E., & Bird, L. (2005). Autoimmunity Nature, 435 (7042), 583-583 DOI: 10.1038/435583a

ResearchBlogging.org

AG McCluskey (2016). Collateral Damage Zongo’s Cancer Diaries

Best Laid Plans

Best Laid PlansWant to hear a joke?  A really, really good one?  Well I’ve got one for you, and it’s a cracker.  It’s one of those jokes that’s a bit dark.  A bit sick, if I’m honest.  And it’ll both tickle your funny bone, and leave you outraged.  Hopping mad, even.

Believe me.  When I heard it, the first thing I did was laugh out loud.  And then I got angry.  Really, REALLY bloody angry.  And the best of it is, that I am the butt of this particular joke.  Me, personally.  I’m the punchline.  Still want to hear it?  Well, here goes.  I just saw this headline in the Guardian:

Revealed: cancer scientists’ pensions invested in tobacco

Yup.  You read that right.  Like most other workplaces, researchers who work in UK universities – researchers like me – have a pension scheme.  Ours is called USS (University Superannuation Scheme) and it is used by the majority of universities in the UK.  So, every cancer researcher based in a UK university uses this scheme.

And, unknown to us, it seems that our scheme has been investing in the tobacco industry for years.  So, every university-based cancer researcher in the UK has, unwittingly, been indirectly profiting from cigarette sales.

Good joke, eh?  Isn’t that a doozy?

Now to say that I am unhappy about this particular state of affairs would be an understatement.  I’m not so much unhappy, as hopping bloody mad.  I’ve spent 20-odd years trying to develop new treatment options for cancer.  So, it’s more than a little galling to discover that I’ve actually, in all that time, been a total hypocrite.

When I retire and start to claim my pension, some of that money will be derived from the World’s most infamous cause of the very diseases I spent a career trying to treat.

I. Am. Not. Happy.

How could this have happened?  What were the directors of the pension scheme THINKING?  Well.  It’s pretty obvious, really.  They were thinking about one thing, and one thing only.  Profit.

We live in an age of Free Market Capitalism, where the only important consideration in any business, in any industry, is The Bottom Line.  Are you in the Red, or in the Black?  And how much are you in the Red or Black?  Profit is King.  It trumps all other considerations.  Morals?  Ethics?  Workers’ rights?  Pah!  As long as you’ve got a nice, fat number in the Plus column, then you’re laughing, right?  Job done.

And if you’ve gotten that number using methods that go against the fundamental principles of your stakeholders?  Who cares?  Screw ’em!  What are they going to do?  Give the money BACK?

So.  Was I surprised by the discovery that USS profits from tobacco?  Yes I was, naive fool that I am.  But was I shocked to the core of my being??  No.  It’s repugnant, but not shocking.  I know how the world works.

But that doesn’t make it RIGHT.  And it doesn’t mean that I just have to shrug and accept it.  This is wrong.  Plain wrong.  And I need to try and change it.  I don’t know how.  I don’t know if I can.  But I have to try, at least.

This is not over.

 

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ResearchBlogging.org

AG McCluskey (2016). Best Laid Plans Zongo’s Cancer Diaries

Patent-ly Obvious…?

Patent-ly ObviousSomething important happened a few months back.  Something which you probably don’t know anything about, because it wasn’t given the prominence it deserved.  But you should know about it, because it could, potentially, impact every single one of us.

An Australian grandmother won a landmark legal case, which has major ramifications for scientific research.  And what did she win?

She won the right for Australians to own their own bodies……..

Say……….WHAT????  What the hell does THAT mean??  Of course Australians own their own bodies!  They’re not slaves!

Ah……but that’s the thing.  Up until she won that case, there were people in Australia who didn’t own their own body….at least, not all of it.  There were teeny weeny bits of every Australian that actually, legally, belonged to someone else.  And it’s not just Australians….there are literally billions of people in the same situation.  Even YOU, sitting there, reading this may not legally own all of yourself.  Maybe even ME, as I write this, may not own all of myself…..

Let me explain.  In my last post, I spoke about the way that scientists are starting to identify and characterise tumour-specific genes and gene mutations, which they will use to develop new therapies and improve treatment planning.  Which is all very well and good, obviously, but it raises an interesting question.  One which has probably never occurred to most people before.

Who owns these genes?

“Huh?” I here you ask, “What do you mean, who OWNS them?  How can anyone “own” a gene?”  Well, that’s a good question.  And it takes us into a very tricky, and VERY controversial area:  Gene Patenting.

In one sense, it sounds like madness.  How can you patent a human gene?  After all, these tumour-specific genes are present in cancer patients, aren’t they?  They aren’t artificial or synthetic.  They are part of the patients’ genetic makeup.  They are entirely natural.  So, how could it be possible for another person or business to OWN them?  It would mean that a cancer patient’s genome didn’t belong to them.  Part of their genome would actually belong to some other person or persons.  How the hell could that be possible?

Well, as mad as it sounds, this is EXACTLY what happens.  Many of the genes which have been identified – genes which are an entirely natural part of the human genome – are currently under patent.  They are owned by Biotech companies who are able to profit from their commercial exploitation.

But….how can this be??  How can you patent a naturally occurring gene?  And how can you make money from it?

Well……technically you can’t.  A patent only covers a new, novel concept or invention.  Therefore, any organism which is found in nature cannot be patented.  And this is why you cannot patent a plant or animal which is found in the wild.

So, surely this means that anyone who tried to patent a human gene would be laughed out of the building, right?  Nope.  This is because, in order to identify a gene in the first place, you have to use some sophisticated scientific techniques, which require specialised Hi-tech equipment.  Both of which had to be thought of.  Both of which had to be created.  And both of which can be PATENTED.  This is the loophole in the patenting laws which Biotech companies can exploit.  While the GENE cannot be patented because it’s natural, the METHOD used to identify it can.  And therefore, anything found by using that method comes under the terms of the patent and can be exploited commercially.  And has been.  Oh boy…..has it ever!  The numbers are a little unclear, but one recent study suggested that as much as 41% of the genes in the human genome have been patented in this fashion!

Now, to say that this had been controversial is a bit of an understatement.  Research scientists object because it stifles their work.  If their research identifies new genes then their work – their effort – will become the property of someone else, so why bother?  Other biotech companies object because it eats into any potential profits from their own products.  Clinicians object because it increases the costs of new diagnostic tests & treatments.  And lots of people across the board (scientists, doctors, patients, politicians, lawyers), they object for ethical reasons and question the legality of a gene – a naturally occurring object – being under patent.

The legal wrangles have been rumbling on for years.  The U.S. Supreme Court ruled against the gene patenting in 2013.  Which is great, obviously, but if the company holds patents in different countries, then the rules need changing in every one.  So the U.S. decision is not enforceable anywhere else.

Which brings us to the Australian case.  In a nutshell, a breast cancer patient called Yvonne D’Arcy brought a case against a Biotech company called Myriad Genetics which holds a patent for the BRCA1 gene.  BRCA1 is involved in DNA repair processes, and BRCA1 mutation has long been known to be associated with an increased risk of hereditary breast and ovarian cancers.    Now, an important point here is that Mrs D’Arcy didn’t have a BRCA1 mutation herself, so her decision wasn’t based on self-interest.  Instead, Mrs D’Arcy objected to this patent on the basis that it increased the costs of genetic screening and could, therefore, mean lower identification rates for women with a predisposition for breast and ovarian cancers.

Initially, the Australian Federal Court ruled in the company’s favour, but Mrs D’Arcy appealed and, at the end of 2015, the Appeal Court ruled that the BRCA1 protein, both the normal active form and the mutant which indicates of susceptibility to breast and ovarian cancer, was not a “patentable invention”.

Success!…and it seems as if the tide is turning.  Already, there are cases being brought in Canada against the patenting of genes and it looks as if the number of patents being filed for genetic sequences is falling worldwide.  So hopefully, one day, private businesses will no longer be able to claim ownership of naturally occurring genes and genetic material.

But until then, the fight goes on….

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Rosenfeld, J., & Mason, C. (2013). Pervasive sequence patents cover the entire human genome Genome Medicine, 5 (3) DOI: 10.1186/gm431

Liddicoat J, Whitton T, & Nicol D (2015). Are the gene-patent storm clouds dissipating? A global snapshot. Nature biotechnology, 33 (4), 347-52 PMID: 25850055

ResearchBlogging.org
AG McCluskey (2016). Patent-ly Obvious…? Zongo’s Cancer Diaries

The One And Only

Marginal Gains 2We are living in an age of transition.  Things are changing in the world of oncology, and these changes are going to have major ramifications for the clinical experiences of future cancer patients.  In the last 30 years, there has been a huge improvement in cancer survival, as shown in the figure.  Now, there are multiple reasons for these improvements.

The development of, and the advances in, diagnostic testing methods has led to earlier disease detection – and earlier diagnosis improves the likelihood of survival.  Also, improvements in scanning machinery coupled to the huge advances in computer technology has led to the development of precise, real time 3D imaging of tumours which has improved the targeting of radiotherapy beams and surgical excision – which has, itself also been proved by advances in keyhole surgery techniques.  Finally, the ongoing development of new chemotherapy drugs has increased the front-line and post-operative treatment options available to clinicians.

Now, all of this has made a difference.  A massive difference.  But more needs to be done.  And one big change that is coming – one that is being mentioned more and more – is the future potential of Personalised Medicine.

And this, Personalised Medicine, is the transition I started this post with.  Clinicians are starting to change the way they think about cancer – about what it is.  Or, to be more accurate, what they are – not a single disease, remember!  And this is leading to changes in how clinicians appraise the different treatment options available.

Now, I’ve mentioned before, cancer is an umbrella term for multiple diseases (see No Cure For Cancer…?).  So, breast cancer is different from colorectal cancer, which is different from lung cancer….etc, etc.  And I also mentioned in No Cure For Cancer…? that lung cancer is not one, single disease either, but can be subdivided into a variety of different cancers, which may require a variety of different treatments.

This type of thinking isn’t new, it’s how clinicians have thought about cancer for many years, and has, therefore, influenced both disease diagnosis and treatment scheduling.  But this is now changing.  It’s becoming more and more obvious that even this myriad of subdivisions is actually overly simplistic and the reality of each patient’s individual disease is much more complicated.

The reason for this is actually very simple.  Each of us is a unique individual.  We have our own unique genetic makeup.  Also, our own individual life experiences mean that the environmental factors we are exposed to, while not completely specific to each individual, are not going to be exactly identical to anybody else’s either.

And, as I’ve mentioned previously, cancer derived from a patient’s own cells.  Therefore, logically, if each patient is unique and their disease arises from themselves then this must mean that each patient’s disease is unique too!  The specific environmental factors each person is exposed to, coupled to the distinct genetic makeup of every individual, means that the risk of developing cancer (in any form) is likely to be different from person to person.  But, also, the way a cancer grows and spreads will likely be different from person to person too, as will the way the tumour responds to treatment, even if the tumours themselves appear to be similar at first.

So, consider the situation where two patients get diagnosed with the same disease, at the same stage, on the same day.  They may appear to be identical and, up till now, this has been the criteria used by clinicians to plan treatment options.  Oh, there will certainly be a whole lot of tests done to look at tumour markers, but on the whole the treatment options that are chosen will be based on size, position & stage of disease.

But actually, there is no guarantee that these two patients will respond to the same treatment in the same way.  This is because their tumours, despite the outward similarity, will actually be very different at an intracellular level.  They will have different genetic backgrounds, different metabolic rates and will be exposed to different environmental factors.  All because of the differences between the patients themselves.

And it is this – the fundamental differences between the tumours – that influence the success of different forms of treatment.  Different chemotherapy drugs target different proteins inside cells (the “Bills” from my Drug Discovery posts).  So, in the example above, the two patients with outwardly similar tumour will be treated with the same chemotherapy drug.  But, if one patient lacks the protein that drug targets, or has a mutation in the gene that makes it (which in turn changes the way it is put together), then the drug won’t work in this patient.  And the tumour will progress in that patient.

But this is starting to change.  Scientists are starting to investigate the tumours from individual patients, in order to identify the specific genes and other tumour-specific markers that can influence drug activity, tumour growth, disease progression etc, etc.  Recently, a major study in Breast cancer identified 93 different genes which could influence Breast cancer growth and development.  Now, these 93 genes don’t all do the same things, they are all different.  And not all 93 have to be present to get the disease.

But the presence or absence of these specific genes can influence how a tumour grows.  So, patient 1 might have, say, 5 of them.  If so, which 5?  What do those individual genes control?  Patient 2, however, has 10 of them – a different subset, with no overlap to patient 1’s markers.  What do these 10 genes control?  How will they influence tumour growth, treatment efficacy, etc?

And this is just the beginning.  Similar genotyping studies are being carried out for other types of cancer.  And it will be the results of these studies that will change treatment planning.  In future, when a patient is first diagnosed, as well as assessing the position, placement and stage of the disease, clinicians will also assess the specific genetic makeup of that individual patent’s individual tumour.  And then they will tailor the treatments they offer, in order to meet that patient’s specific requirements.

So remember:  You are an individual.  Your disease is also individual.  And, in future, your treatment will be individual too.

Welcome to the age of Personalised Medicine.

 

…………………………………….

Nik-Zainal, S., Davies, H., Staaf, J., Ramakrishna, M., Glodzik, D., Zou, X., Martincorena, I., Alexandrov, L., Martin, S., Wedge, D., Van Loo, P., Ju, Y., Smid, M., Brinkman, A., Morganella, S., Aure, M., Lingjærde, O., Langerød, A., Ringnér, M., Ahn, S., Boyault, S., Brock, J., Broeks, A., Butler, A., Desmedt, C., Dirix, L., Dronov, S., Fatima, A., Foekens, J., Gerstung, M., Hooijer, G., Jang, S., Jones, D., Kim, H., King, T., Krishnamurthy, S., Lee, H., Lee, J., Li, Y., McLaren, S., Menzies, A., Mustonen, V., O’Meara, S., Pauporté, I., Pivot, X., Purdie, C., Raine, K., Ramakrishnan, K., Rodríguez-González, F., Romieu, G., Sieuwerts, A., Simpson, P., Shepherd, R., Stebbings, L., Stefansson, O., Teague, J., Tommasi, S., Treilleux, I., Van den Eynden, G., Vermeulen, P., Vincent-Salomon, A., Yates, L., Caldas, C., Veer, L., Tutt, A., Knappskog, S., Tan, B., Jonkers, J., Borg, �., Ueno, N., Sotiriou, C., Viari, A., Futreal, P., Campbell, P., Span, P., Van Laere, S., Lakhani, S., Eyfjord, J., Thompson, A., Birney, E., Stunnenberg, H., van de Vijver, M., Martens, J., Børresen-Dale, A., Richardson, A., Kong, G., Thomas, G., & Stratton, M. (2016). Landscape of somatic mutations in 560 breast cancer whole-genome sequences Nature DOI: 10.1038/nature17676

Morganella, S., Alexandrov, L., Glodzik, D., Zou, X., Davies, H., Staaf, J., Sieuwerts, A., Brinkman, A., Martin, S., Ramakrishna, M., Butler, A., Kim, H., Borg, �., Sotiriou, C., Futreal, P., Campbell, P., Span, P., Van Laere, S., Lakhani, S., Eyfjord, J., Thompson, A., Stunnenberg, H., van de Vijver, M., Martens, J., Børresen-Dale, A., Richardson, A., Kong, G., Thomas, G., Sale, J., Rada, C., Stratton, M., Birney, E., & Nik-Zainal, S. (2016). The topography of mutational processes in breast cancer genomes Nature Communications, 7 DOI: 10.1038/ncomms11383

ResearchBlogging.org
AG McCluskey (2016). The One And Only Zongo’s Cancer Diaries