Kitchen cupboard “cures” – number one: turmeric

Wouldn’t it be great if we could cure all our ills with ingredients we can find in our kitchen cupboard? Plenty of people claim that it can be done and with the popularity of ‘natural’ medicines it’s not just your Nana who recommends it because that’s what her Nana taught her.

Kitchen cupboard remedies have become so mainstream that they become potentially dangerous when recommended for life-threatening diseases such as cancer. In fact, just a few months ago the Express asked “Can turmeric really cure cancer? Woman says benefits of golden spice ‘cured’ her disease”.

the express
Headline from the Express: “Can turmeric really cure cancer? Woman say benefits of golden spice ‘cured’ her disease”

But sometimes we wonder, if so many people believe it, maybe there’s really something in it?

In this series I will cover kitchen cupboard “cures” to investigate the claims made, and what the science really says. The series begins with the tasty Indian spice turmeric.


Turmeric is often reported as some sort of wonder spice. People who promote its use claim turmeric is anti-inflammatory, reduces cholesterol, treats diabetes, prevents Alzheimer’s disease and both prevents and cures cancer.

glass jar of orange coloured ground turmeric on a tea towel with a wooden spoon on the worktop next to it and turmeric on the spoon and counter

But actually, while this seems like a bizarre old wives’ tail, there is evidence supporting some of the claims for turmeric. The active ingredient in turmeric is curcumin or diferuloyl methane. Experiments in the lab show that curcumin alters the expression of genes in cells and some of these genes are related to specific pathways. For example, curcumin alters the expression of proteins related to inflammation in rat liver cells in a petri-dish and also alters the production of cholesterol in cells. Curcumin supplementation might also help manage some of the side effects of diabetes but only in conjunction with standard therapy. There is even some early evidence from mice with Alzheimer’s disease that curcumin can slow cognitive decline.

However, the science is also quite complicated. When it comes to cancer there is some evidence that curcumin can slow the growth of cancer cells in the lab but plenty of things slow cancer growth in the lab and never go on to prove useful therapies. Having said that, some clinical trials have shown that curcumin might one day prove useful as an adjunct to some cancer treatments in some cancer patients with some types of cancer.

The Express article above did discuss a case of a woman with myeloma, a type of blood cancer. This article was based on a single case published in British Medical Journal Reports in which a patient who had been on conventional treatment for many years suffered a relapse and was advised that there was nothing else doctors could do to help treat her cancer. The patient decided to take 8g chemical curcumin in tablet form per day in the hope it would treat her cancer. Her cancer has subsequently stabilised. This is a potentially interesting case – however it is only one single case that has been observed. Subsequent studies have not been done to investigate why this patient stabilised and there is insufficient evidence that it was the turmeric that was responsible. In fact, there are rare cases in which cancers such as myeloma can go into spontaneous remission without treatment and doctors believe this might be due to the patient’s own immune system targeting the cancer cells.

Important caveats

It would seem that the early research is fairly promising, however there are some very important caveats to remember here. So far, these studies are largely done in cells in a petri-dish or animals like mice or rats. We are not yet able to translate the findings to humans and we’re a long way from finding useful therapies using this compound.

Importantly, the studies use chemical curcumin rather than dietary turmeric and usually have specific measured doses. If curcumin becomes a useful therapy, the dose will change between different diseases and different patients. There is no evidence supporting the use of turmeric in isolation to treat disease. In all studies it is used as a supplement to standard therapy.

Clear capsules with orange powder inside

Medical treatments should always be managed by a medical professional. Any ‘herbal’ remedy has the risk of interacting with conventional drugs. In the case of curcumin research has shown that the chemical can inhibit some cancer treatments so it is important we understand the role curcumin plays in reacting with other medications before using this to treat patients.

It is because of this risk of interaction with other medications that it is really important patients taking any herbal remedy supplements speak to their doctors about whether these supplements might harm themselves or the efficacy of their treatments. It is important to note that many supplements are not fully regulated and therefore may contain ingredients that cause harm. For example, some curcumin supplements have been shown to contain anti-inflammatory drugs which can cause liver damage if taken in excess.

Summary: while there is some early evidence the active ingredient of turmeric might one day prove a useful supplement to conventional therapy we’re a long way from this being clinically useful. We need much more research to confirm the efficacy of curcumin and to establish which compounds work best and at which doses.

Next week I’ll be writing about Rosemary. If you have any specific requests for a Kitchen Cupboard “Cure” for me to cover, please leave a comment or send me a tweet @AliceEmmaLouise.

For more information on turmeric and cancer you can see CRUK’s review.





Skincare, anti-aging (and cancer)

The world of skincare is not a place for the faint-hearted. It is such a dizzying mix of advice and recommendations, advertising and ‘science’ that any wander through this world leaves you feeling like you are not doing enough for your health or appearance. The only way to make yourself feel better, it would seem, is to spend sometimes hundreds of pounds on products you will use religiously for a few weeks before you end up exhausted by all the time you’re spending slathering on potions, oils and creams.

Why do we do it?

There are a range of reasons we feel we have to invest time, money and energy into our skin. One of the main reasons seems to be to maintain a youthful appearance for longer. Anti-aging is a huge part of skincare marketing and people (women especially) are targeted from an early age to start protecting their skin from the effects of aging.

The science of aging

There are two types of aging – intrinsic and extrinsic.

Intrinsic aging is the type that is genetically accounted for. It happens naturally pretty much no matter what you do. This is the kind of aging that leads to changes in skin elasticity. This type of aging is also called chronological aging and is the one you cannot really do much to change.  The characteristics of intrinsic aging include smooth, unblemished skin with a loss of elasticity, fine wrinkles and paling of the skin. The skin gets thinner and the small blood vessels in the skin reduce in quantity.

In addition to the natural course of aging, we also have extrinsic aging. This is the one our behaviour has a say in. By far, the two biggest factors which cause extrinsic aging are smoking and exposure to UV light.

Smoking reduces the elasticity of skin and reduces collagen levels in the skin. This means the skin gets hardened, slack and rough. We have evidence from multiple studies over a number of years showing that smokers have increased wrinkling compared to non-smokers. The evidence is consistent and overwhelming – smoking tobacco increases skin aging.


Exposure to UV light from the sun is thought to account for up to 90% of visible skin aging. UV light causes an increased level of specific proteins in the skin called enzymes. The enzymes that are increased in skin exposed to sunlight are responsible for degrading important connective tissue. After repeated exposure the skin starts to sag and to form wrinkles. Sunlight exposure increases the production of reactive oxygen species (ROS) and free radicals in the skin. ROS and free radicals damage the DNA which increases your risk of skin cancer, but they also increase the levels of those degrading enzymes even more. In addition to all of that, UV radiation interferes with the immune system and may even prevent cell death in sun-exposed skin which can also contribute to an increased risk of skin cancer. The characteristics of photoaged skin include nodular, leathery, blotchy skin with coarse wrinkles and furrows. The skin has irregular pigmentation and obvious marking on the skin and the elasticity is severely damaged. Blood vessels become dilated and there is pronounced inflammation.

What works?

It should be clear, now, that the two most useful ways to prevent visible skin aging are to minimise intake of cigarette smoke and to minimise skin exposure to damaging UV rays.


To protect your skin from UV damage, applying a daily sunscreen with a high factor SPF and high-quality UVA protection (4 stars or above). SPF protects your skin from burning and from the damage associated with that but it does not protect against UVA radiation. UVA damage is invisible, although it does cause darkening of pigmentation, and is very deeply penetrating. You need a sunscreen that protects against both UVA and UVB damage.

image of a person's knee with white sunscreen and a hearth drawn into the sunscreen

Topical Retinoids

While most skincare products have very little evidence supporting their use in preventing or reversing the signs of aging, there is one active ingredient that does seem to help.

Retinoids are a family of chemicals which include retinol (vitamin A) and similar compounds. The potential of retinoids in treating aging was discovered in the 1980s when scientists treating photoaged mice noticed repair of the skin and reduction in wrinkling. We now know that retinoids encourage cell growth and can reverse some of the effects seen in photoaged skin and you can buy skincare products which have retinoids in them. There are two downsides to using retinoids on your skin – firstly, retinoids can cause some sensitivity making the skin red and sore which means some people cannot use it at all and most people need to build up their usage from a low dose (0.1%) used infrequently (1-2 times per week). Retinoids can also make your skin more sensitive to UV damage. This means if you are using retinoid skin products you need to be extra careful about staying out of the sun.

Prevention is better than cure

Ultimately, the best thing you can do for your skin to prevent visible aging is to protect it from harmful damage caused by smoking or sun damage. Of course, if you enjoy the relaxation of using different products on your skin, then go right ahead. But the best way to protect your skin is to use a decent sunscreen and to refrain from smoking.

You will also be doing wonders for your risk of lung and skin cancer!


Read more about skin cancer here: 




Trends in Pseudoscience: Raw Water


Water consciousness movement/raw water

What is it?

The water consciousness movement is a trend towards eschewing tap or bottled water for drinking and instead turning to unfiltered, unpasteurised, unsterilised spring water.

But why?

Proponents and, indeed, suppliers of this trend say that tap water in the US has been filtered – removing bacteria and minerals that they believe benefit the body. One supplier of ‘raw’ or ‘live’ water, Live Water, claims that “you can attempt to remineralize filtered water, but those minerals will never be bio-available like in fresh living spring water”. The bacteria content in ‘live’ water is lauded with Live Water announcing “there could be countless other beneficial microbes present, scientists just haven’t discovered yet”. They claim that beneficial bacteria, which they refer to as probiotics, are crucial for the proper digestion of food and the promotion of good health. Not only that but some raw water proponents are fearful of fluoride present in tap water. The founder of Live Water, Mukhande Singh, told The New York Times “Call me a conspiracy theorist, but it’s a mind-control drug that has no benefit to our dental health.”

And why not?

The filtering process applied to US tap water is and important step in making water that is safe to drink. It removes bacteria which can include organisms like E.coli but also parasites and viruses. A telling indication of the microorganisms present in ‘raw’ water comes from Mukhande Singh who told The New York Times of his company’s ‘live’ water: “If it sits around too long, it’ll turn green. People don’t even realize that because all their water’s dead, so they never see it turn green”. Water going green over time is a sure sign that something is growing in it. The water is alive, just not in the way that Mr Singh claims. Water borne diseases are not a problem for many Americans, these days, because we solved the problem with the availability of clean drinking water. The blight of the 1800s, cholera, a disease caused by water contaminated with a bacterium called Vibrio cholerae taught us a lot about the dangers of drinking unsanitary water. Sufferers of the ‘blue death’ often succumbed to a rapid death caused by severe dehydration, a consequence of incessant diarrhoea and vomiting.

Scanning electron micrograph of the rod shaped cholera bacteria (Vibrio cholerae). Source:

US tap water is carefully regulated to ensure safe levels of microorganisms. US tap water is fluoridated which is scientifically proven to improve dental health. But there’s another benefit to drinking water that is regulated to prioritise health and safety. These regulations are subject to changes based on the evidence as our scientific understanding of certain contaminants develops. For instance, arsenic naturally occurs in water. Since the 1960s the regulations sustained arsenic below 50ug/L but by 2006 all drinking water in the US was required to have a level of 10ug/L or less. Studies show that this reduction in the regulated level in US drinking water has resulted in a reduction in the diagnosis of lung, bladder and skin cancer each year.

‘Raw’ water, is not regulated in the same way. The contamination of each ‘batch’ of water might not even be monitored. Not only might customers be drinking dangerous contaminants – they have no idea of which contaminants and at what level might be present in the ‘raw’ water they consume.

A list of alternative cancer therapies and a Good Thinking Society

Recently I worked on an interesting project with the Good Thinking Society.

The Good Thinking Society are a great charity who are small in size but are making great waves. The charity was founded by Simon Singh and their goal is “to encourage curiosity and promote rational thinking”.

One thing the Good Thinking Society does excellently is working in the medical field – they have been fundamental in changing the environment of NHS funding for treatments which lack scientific support for their use.

In 2010, The House of Commons Science and Technology Committee reported that homeopathy is no better than placebo. Despite this, this scientifically implausible treatment continued to be funded on the NHS to the tune of three to five million pounds per annum. This is a figure that the Good Thinking Society determined after working systematically through each CCG in the UK to identify which of them continued to fund homeopathy and how much they spent. Good Thinking Society supported many of those CCGs still funding homeopathy in reviewing their funding policies and succeeded in initiating the removal of this funding in many areas across the UK. They have also been instrumental in NHS England calling for homeopathy to be added to the NHS Blacklist of items which cannot be prescribed by GPs.

Good Thinking Society have some excellent resources on specific alternative therapies which you can find under their heading ‘Good Thinking About’. In particular they have an excellent primer on Gerson Therapy, a ‘treatment’ promoted as a cure for cancer which I have discussed here before.

Recently, I helped the Good Thinking Society compile a list of treatments which might be offered by alternative practitioners to vulnerable cancer patients. The list brings together a summary of the evidence for each treatment and outlines some of the potential risks and dangers of those treatments.

Here is a sample from this list:

Cancer list

Go take a look at their website and the list of alternative cancer treatments. And while you’re there – donate to their cause. They exist on donations and they need your support.

Autism Spectrum Disorder (ASD) and Aluminium

Recently, Professor Chris Exley from Keele University claimed that his research “provides the strongest indication yet that aluminium is a cause of ASD”. In an article originally published in the Hippocratic Post and reproduced by the Daily Mail, Exley claimed that brain tissue from five donors diagnosed with Autism Spectrum Disorder (ASD) contained “some of the highest values yet measured in human brain tissue” of aluminium. He postulated “perhaps we now have the link between vaccination and autism”.

This controversial claim comes almost two decades after Andrew Wakefield published the now discredited and retracted research into ASD and the measles, mumps and rubella (MMR) vaccine which was linked to a decline in vaccination rates and recent outbreaks of measles.

I spoke to Tom Chivers from Buzzfeed about my concerns with this paper. In his article you can read concerns from myself and eminent academics Professor Dorothy Bishop and Professor Jonathan Green, renowned experts in neurodevelopmental biology and child and adolescent psychiatry respectively.

Such a controversial claim which can affect the health of children worldwide really needs some solid supporting evidence. So, let’s take a look at the paper itself.

Aluminium in brain tissue in autism

The paper is due to be published in the Elsevier Journal of Trace Elements in Medicine and Biology in March 2018 and the accepted paper is available to read online. The authors introduce the study saying “we have measured aluminium in brain tissue in autism and identified the location of aluminium in these tissues”. The paper can be split into two sections.

Section one

The authors measured the levels of aluminium in brain tissue taken from five donors aged 15 to 50 who had all been diagnosed with ASD prior to their deaths. They took 0.3g tissue samples for four (occipital, frontal, temporal and parietal lobes) or five (they added hippocampal tissue where it was available) brain regions. They measured three replicates of each brain region using spectrometry.

The problems with the methods and data from this section are three-fold:

  1. The authors took samples from only five brains – all five donors had died with a diagnosis of ASD. There were no healthy control samples used anywhere in this study. This is a particular problem because without a healthy control, it is impossible to really say whether the aluminium levels measured in the brains of the donors is actually higher than that of a non-autistic brain. There is nothing to compare the measurements to.
  2. Importantly, the authors do not provide information on how the donors died. We have to take their word that the cause of death does not account for variation in brain levels of aluminium. An important part of the scientific publication framework is that this sort of information should be easily available to the reader. We need to be able to come to our own conclusions based on the data presented. That this information is missing is quite concerning.
  3. Finally, in some cases the three replicates from each brain region per donor did not corroborate each other. In one case there were three measurements of 0.01, 0.64, and 18.57μg/g. Similarly, another donor had measurements of 2.44, 1.66, and 22.11 and another, 1.71, 1.64, and 17.10μg/g. The authors averaged these data, however such an average does not represent any of the three measurements and is an inappropriate way to analyse these figures. In fact, such variation between measurements might even hint at an anomalous result, which requires further assessment to adequately rule out.

Section two

In the second section of this paper the authors took samples of brain tissue from the valuable Oxford Brain Bank. Again, they took tissue from a selection of donors who had been diagnosed with ASD before their death. Again, the authors failed to express how the donors died. The authors took samples from 10 donors aged 14 to 50 and stained them with a dye that specifically sticks to aluminium. The dye can then be visualised with a fluorescent microscope to see where in the brain tissue it can be seen.

Again, the issues with this section are three-fold

  1. This section also lacks the use of ‘healthy’ controls. The authors do show presence of aluminium in the tissue samples of their ASD donors but we have no indication of whether this is, in fact, more than we might see in a healthy brain.
  2. This section is also lacking a positive control – a sample that has a known amount of aluminium in it. This is important for interpreting the staining of the dye; if the dye is very sensitive then we might see loads of staining for just a small amount of aluminium. We need to compare it to a known sample.
  3. Later in their interpretation of these data the authors discuss the presence of aluminium in specific cell-types which they surmise might be lymphocytes. However, they do not use any detectable markers to propose this, they base it only on how the cells look. Cell appearance (also known as morphology) is a useful initial indicator of cell-type but it is important to confirm this using specific markers for those cells.
A figure taken from the paper which apparently shows the accumulation of aluminium in specific cell types

Overall the data from this paper is insufficient to draw the conclusions made in the Hippocratic Post and The Daily Mail and it is my concern that such reporting is irresponsible. While the two articles conclude that aluminium present in the brains of people with ASD might be caused by vaccination, there is no investigation whatever into the source of such aluminium in this study. There are no data presented in this paper sufficient to implicate vaccination in these findings. To draw the link between aluminium in the brain of people with ASD and vaccinations makes for a striking headline but the data do not support this claim and it could therefore be viewed as scare-mongering.

I am surprised that this paper was published in the Journal of Trace Elements in Medicine and Biology because the lack of control data makes the findings inconclusive. I am yet more surprised that this inconclusive data has been reported in such a paper as The Daily Mail, when such media attention can lead to parents making potentially dangerous decisions for the health of their children.

Please let me know below what you think about the reporting of this science?

How many mutations does it take to create a cancer?

Last week I wrote a post all about how we understand cancer to arise. I explained how mutations in certain genes for certain proteins can drive cancer and I explained some of the important families of proteins such as oncogenes and tumour suppressors.

But even that complicated post was an over-simplification. Sure, a single mutation in a single gene for a single protein might cause cancer, but actually we know that many cancers have several mutations. Sometimes, several hundred mutations.

Several hundred mutations

many mutations per cancer
Image adapted from this paper. A graph showing a number of non-synonymous mutations per tumour against tumour types ranging from colorectal cancer to glioblastoma. (See the text for some example figures).

The above is an image which shows just a few examples of some cancer types and the number of mutations you might expect to find in them. Recognise the word non-synonymous from last week? Non-synonymous mutations are those which cause a change in a protein. Whereas synonymous mutations are effectively “silent” (they don’t change a protein) so we tend to focus on non-synonymous ones when it comes to disease. You can read more about them here.

From the image you can see that some types of cancers can have several hundred mutations per tumour – colorectal cancer for example can have between 500 and 1200 mutations. Lung cancer can have between 100 and 200 (interestingly this is much lower for lung cancer in the “never-smoked” category which has a considerably smaller number of 25) and breast cancer between 25 and 100 mutations per tumour.

The problem

What this means is that when it comes to understanding what drives cancer we need to know how many of these mutations are actually relevant to the disease. Do they all contribute to “driving” cancer or are some of them “passenger” mutations? If only a few contribute, then how many?

Often, we treat cancer by designing drugs which target specific proteins. If we suspect a cancer is “driven” by an overactive protein then we can treat patients with an inhibitor of that protein – something that blocks the protein’s function. But for us to do this, we need to know which mutation, potentially hundreds, is actually relevant. It’s like trying to find a needle in a haystack.

The study

The paper published in October 2017 in Cell is an analysis of 7,664 tumours across 29 different tumour types. They looked at all of the mutations each of those tumours had and focussed on the non-synonymous ones, the ones that actually change the proteins inside the cell. But they knew that even with protein changes, not all of the mutations present actually cause cancer. They wanted to establish how many might be responsible for the disease.

“Normal” cells acquire mutations all of the time but this happens at random so sometimes it will affect proteins and sometimes it won’t –  we get a reliable mixture of non-synonymous and synonymous mutations that are all mostly harmless even if there is a change in a protein. This is useful information because we can establish an “expected” ratio between the two. In cancer cells, the mutations that change proteins and allow a cell to survive and grow more than it should (i.e. the mutations that drive cancer) are passed on to more cells as the cancer cells replicate. This means you get a skewed ratio in cancer cells – more non-synonymous mutations than synonymous ones. By figuring out how many more mutations there are than we expect from the “normal” cells we know that those are the ones allowing cells to replicate in an uncontrolled way – therefore those are the ones that are driving the cancer.

And that’s exactly what the authors of this study did.

What they found

What they found was that although some cancer cells have hundreds of mutations, only a few of those actually drive the cancer. The average number of cancer drivers per cancer type is just four and the numbers only range from one to ten. So, we can narrow our focus to between one and ten mutations per tumour. We just need to figure out which ones.

This is phenomenally useful information because we can then build further on this knowledge to understand which mutations are the common driver mutations and focus our drug development on those specific mutations. We have a significantly smaller haystack and we can start to really get very specific with our cancer therapies! The better our understanding of how cancer really works, the more complete our understanding of all of the complicated processes involved, the better able we are to design clever therapies that really benefit patients.

What drives cancer?

When it comes to understanding cancer, getting our heads around the complicated process of how it forms in the first place is vital. When we know what drives cancer then we can figure out how to diagnose it and ultimately, how to treat it.

So far, research has shown us that the vast majority of cancers are caused by some level of genetic mutation. This is something we’ve known for a long time and something we use in order to treat different types of cancer. For example, a reasonable proportion of breast cancer patients have a mutation in the gene for a particular protein called HER2 making this protein more abundant than it should be and allowing cancer cells to grow and grow. So scientists have designed a therapy that blocks, or inhibits, HER2 – a drug called Herceptin. The cancer cells have been relying on HER2 for their growth, they’ve becomes entirely dependent on it which means when we treat patients with Herceptin, HER2 activity is reduced and the cancer cells die.

Another thing we know about cancer, is that it’s hugely genetically unstable. This means cancer cells acquire loads and loads (sometimes many hundreds) of new mutations as the disease progresses. What is important is to understand which of these many mutations are actually fundamental to the survival of the cancer. Which ones are truly driving the disease, allowing it to survive and progress and spread?

This can be particularly complicated for us to understand because a mutation in one gene can do lots of different things.


First things first, let’s define what a gene is. When it comes to DNA we can think of an organism’s entire genome like a recipe book. The entire human genome book allows our cells to work together to cook an entire human. If we were cooking a really complicated meal like Christmas dinner we would need to cook all the different components and bring them all together to make the meal. You have to cook the main dish and all the side dishes, your carrots and parsnips and brussel sprouts, maybe two kinds of potatoes and a soup for the starter. Every person’s Christmas dinner might look slightly different but we all agree it’s a complicated meal and there are lots of components. The human body is also pretty complicated and is made up of components. A human body is made up of organs, which at the most basic level are made up of cells. Your cells are kind of like the ingredients for each dish in your Christmas dinner. Your organs are kind of like those individual dishes. They all come together to make the whole human. So, in order to make such a complicated thing, we need lots and lots of recipes. Within the human genome we have 23 pairs of chromosomes, which we might think of as chapters of the recipe book. Within each chapter are individual recipes, or genes, which allow cells to make for individual building blocks (ok, ok, I’m mixing my metaphors…).

The basic building blocks in the human body are cells. Cells come together to make our organs, and organs come together to make a human. But our cells need to do specific jobs depending on what kind of cell they are; they need to communicate with one another within the organs they are a part of. This is what makes our heart cells contract all together to pump blood around the body or it allows all of our lung cells to know that they’re supposed to be lung cells. This communication is done through proteins, which can pass signals along complicated pathways transmitting the message from protein to protein and giving each cell instructions on how to function. A single gene is a recipe for an individual protein. Each gene is made up of many thousands (depending on the protein size) of what we call bases which are signified by the letters A, T, C and G. There is an extra layer of complexity as the code that makes up a single gene is organised into groups of three letters each group referred to as a codon. Each codon codes for a single amino acid and these amino acids build up in long sequences to eventually form proteins.

DNA to protein
In order to convert the genetic code the cell must convert DNA into an intermediary molecule called RNA. This can then be translated into protein. Each ‘codon’ (three letters) is a code for one amino acid which build up in sequences to make proteins.

A mutation is change in this code. And that tiny change can have a number of outcomes.

Ultimately – the ones we’re worried about are those that change how particular proteins behave.

How do protein mutations drive cancer?

On a very basic level, proteins basically control everything. They regulate which cells go where, how big cells grow, how much cells replicate and how cells function within their organs. Some proteins are crucial to very specific pathways related to cell survival and cell replication (referred to as proliferation). These proteins we refer to as oncogenes or tumour suppressors. They carefully regulate how cells grow and survive. If these pathways become deregulated, cells can grow out of control and survive when they shouldn’t. This is how cancer forms. These pathways, and therefore these particular proteins, are fundamental in driving cancer. Many of the most commonly mutated proteins in cancer are either oncogenes or tumour suppressors. But what exactly are these proteins?

An oncogene is a protein which promotes cell growth and cell survival. In normal cells these proteins are carefully regulated. They become activated and they pass on the message to tell the cell to grow or survive and then they get switched off until they are next required. Oncogenes can be mutated in such a way that their activity is increased – either there are loads of copies of them all passing on the “grow and survive” message at once, or they are unable to be switched off and they are constantly telling the cell to grow and survive. In this way, a mutation in an oncogene can drive cancer.

A tumour suppressor is one of those proteins that helps regulate the growth and survival pathways. Tumour suppressors can switch oncogenes off, or they can oppose them by sending the opposite message. They serve to slow down the “grow and survive” message and keep our cell growth and survival finely tuned. In this way, when functioning properly, tumour suppressors prevent cancer. A mutation that blocks these proteins from doing their job will therefore promote cancer.

This is adapted from my PhD thesis. Here are two pathways with the various proteins that ‘transmit’ the signal through a cascade of activation. One pathway leads to cell replication (proliferation) and the other to cell survival. Some of these proteins are particularly crucial in promoting these pathways – PI3K and Ras, for example, are oncogenes. Some of these proteins are crucial in regulating or slowing down these pathways – PTEN, for example, is a tumour suppressor.

Different types of mutation

This complexity of the genetic code means there are number of different ways in which a gene can be mutated.

We can split these into two broad groups – synonymous and non-synonymous. Synonymous mutations are ones where the mutation doesn’t lead to change in the sequence of amino acids in a particular protein. They are effectively silent mutations because they don’t change proteins.

But many gene mutations are non-synonymous; one way or another, they cause a change in the protein produced by that gene.

Of these we can have:

Missense mutation is a mutation where one amino acid is switched out for another. The importance of that particular amino acid to that particular protein designates whether or not this change has a big impact on the protein function. It can increase activity of an oncogene, or it can prevent an active oncogene from being switched off. Alternatively, it can block the action of a tumour suppressor.

Nonsense mutation is a mutation which leads to termination of the protein production at that position in the code, leading to a shortened or truncated version of the protein which may severely alter the ability of that protein to function normally. A truncated tumour suppressor, for example, isn’t able to switch off cell growth and might promote cancer.

Insertions/deletions occur when a few letters are added to or removed from the code which can completely alter the entire remaining sequence leading again to protein truncation. Large deletions can remove entire genes preventing the production of that entire protein. This can include duplication mutations when a particular region of DNA is duplicated which may enhance or reduce the activity of a protein.

Large-scale mutations in chromosomal structure – these can be very complicated including the amplification of entire genes giving you far too many copies of a particular protein. They can also create entirely new proteins by fusing two separate genes together.

What does all this mean?

Hopefully it’s clear that the variety of mutations and proteins involved in driving cancers is quite complicated and that makes understanding cancer difficult. However, we might also see opportunities for using knowledge to treat cancers. If we can establish how frequently a particular cancer is cause by an overactive oncogene then we can start to find treatments that block or inhibit those oncogenes. These are strategies that have led us to discover drugs like Herceptin, which blocks the oncogenic HER2 receptor I talked about at the beginning of this post. But it also means we need to fully understand which mutations drive cancer in order to establish treatments for them.

Next week I’m going to talk about a particular study that looked at these driver mutations that was published just this month. The researchers wanted to get a more complete picture of how many proteins we might need to target in order to effectively treat specific types of cancer and what they found was really interesting.

For now, I’d love some feedback on this post because it’s quite science heavy – if there’s anything I could have explained better or in more detail then let me know in the comments and maybe I can write more on these topics in the future.


*edited to correct some of the HER2 science – thanks to my good friend Dr Jenny Smith-Wymant for pointing out my mistake.