In this edition of "What the Hell? - Cancer" I will going through how cancers are diagnosed. This will hopefully give you an idea about what the different stages of cancer are and how each cancer is graded differently. 

NOTE: All my examples will be using breast cancer because it is the cancer type I study and am most familiar with.

Before I begin I want to just clear up the differences between primary tumours, secondary tumours and primary secondary tumours. 

• Primary tumour: tumour which has originated in one location 
• Secondary tumour: tumour which is derived from the primary tumour (share genetic etc. similarities) but is found in one or more locations in different locations in the body from the primary tumour (happens usually by metastasis).
• Primary secondary tumour: tumour which has originated independently from another tumour in a different part of the body at a different time to the other tumour. E.g a breast cancer patient is discovered to have colorectal cancer (CRC) after diagnosis with breast cancer however the tumours are not related (genetically etc.). The CRC tumour developed independently from the breast tumour. 

Cancer diagnosis is a tricky business. If you read my awareness posts you will see the signs and symptoms of a lot of different cancers. You may have noticed that a lot of the signs and symptoms are generic for example bloating, intestinal discomfort, a prolonged cough etc.

Tumours need to be detected before you can take a biopsy etc. These are the main ways tumours are detected (but not the only ways). Apologies for the explanations. While I learnt all this in my masters (woo nuclear physics) I am no physicist... 

• Ultrasound: this technique is based on sound waves. Sound wave are sent into the body and the speed the sound waves move tells you what type of tissue is there. The slower the sound waves the denser the tissue (e.g bone 4080 m/s vs soft tissue 1540 m/s and air 330 m/s). The sound also bounces back from the tissue. The denser the tissue (e.g bone) the more sound is sent back.  An ultrasound machine sends out a pulse which is reflected back to the machine. Depending on the speed of the reflection and how much sound is reflected back this creates an "image". Tumours are denser than normal soft tissue.

 

• PET/CT: this techniques uses a modified type of glucose (18FDG) that comes up black on a PET scan. As tumours use a huge amount of glucose you can infer that places where there are dark areas of glucose are masses of highly proliferating cells. A PET scan takes an image of the body however the resolution is quite low, meaning you are not 100% sure where exactly in the body the tumour is. A CT scan is a much more in depth image of the body, including the organs etc. by fusing the images you get a picture of where in the body this build up of glucose is and where the tumour is. There is one drawback with this method - the bladder. The bladder is where the modified glucose goes to be excreted and therefore you will always see the bladder as a big black spot. This can hinder diagnosing bladder cancer and cancers around that area. 

 

• MRI (magnetic resonance imaging): this technique is based on creating a magnetic field. Interestingly, MRIs look mainly at water molecules. Two magnetic fields are created perpendicular to each other. The first magnetic field forces hydrogen nuclei to align parallel (low energy state) or anti-parallel (high energy state) to the magnetic field. Each tissue type has a certain number of high energy and low energy nuclei. The difference between the two gives each tissue type an "M" value. For example if a tissue had 20 low energy nuclei and 100 high energy nuclei the M Value would be 5 (100/20). The low energy nuclei are then "excited" to high energy nuclei by adding energy. As they return to a low energy state, they release energy. The MRI detects how much energy is released. Different tissues release different amounts of energy, allowing the machine to tell them apart. The second magnetic field allows the MRI to create an image. The MRI does all of this in small sections and creates a picture by building the sections one on top of the other. Nuclear physics everyone! 

Part of what pathologists are looking for when they stain biopsies is structural changes to cells. Cells "adapt" to their environment or from internal cues by changing their structure. There are a number of cellular adaptions which happen normally but can also be due to disease etc.

1. Atrophy: this is when the cells shrink. This can happen in response to not using them (e.g. muscle) or poor blood supply/nutritional deficiency. 
2. Hypertrophy: this is where the number of cells in an organ or tissue increase, mostly seen in skeletal muscle and cardiac muscle. 

The next three are characteristic of pre-cancer cells (i.e. structural changes that can lead to cancer):

1. Hyperplasia: number of cells in organ or tissue increases (similar to hypertrophy).
2. Metaplasia: cells change from one type to another. For example in your oesophagus you have epithelial cells (roughly circular blobs) whereas in you stomach you have mucosal cells which are more rectangular and structured to withstand stomach acids. In Barrett's oesophagus, constant exposure of the oesophagus cells to stomach acid due to acid reflux changes the cells from epithelial to mucosal. Barrett's oesophagus is a risk factor for oesophageal cancer. 
3. Dysplasia: normal cells grow in a disordered way. Instead of growing side by side where all the cells are orientated the same direction, cells grow all over the place.

Change of shape and structure and the number of darkly stained cells allow pathologists to grade tissue samples. Histopathology is based very much on the person and takes years and years to generate enough knowledge to be able to look down a microscope at a purple stained piece of tissue and say "that is a squamous cell carcinoma" (type of skin cancer - don't look up images). There is a lot more to the work of a pathologist but I don't have the knowledge to delve deeper. ​

So what do I mean by stage? Well the stage of the cancer tells you (in general terms) how big the tumour is, if it has invaded locally or systemically and what treatment you should use. 

• Benign: a collection of cells that do not display the hallmarks of cancer and are not likely to grow and invade
• Stage 1: this is the earliest stage of a tumour. The tumour is contained within one area and has not invaded. The tumour also tends to be small in comparison to later stages. 
• Stage 2: the tumour begins to grow and invade into the immediate area around the tumour. 
• Stage 3: the tumour invades locally and is large
• Stage 4: the tumour invades systemically (metastasis) 

Clinicians expand on this and use a system called TNM. This is "Tumour", "Node", "Metastasis". 

• Tumour: numbered 1-4 depending on the tumour stage, the size of the tumour and how much it has spread
• Node: numbered 1-3 depending on is lymph nodes are involved, size, location and how many are involved.
• Metastasis: 0 or 1, either there is metastasis or no metastasis

As I said before each cancer type has slightly different staging criteria. This is due to the type of organ it is in (some organs are smaller than others so a "small" tumour in a large organ is actually quite a big tumour in a smaller organ). The staging also has to take into account where the tumour invades locally and systemically and if lymph nodes are involved. 
​
In breast cancer:

• Stage 1 (T1): is a tumour which is less than 2cm across and a few breast cells are found in the lymph nodes around the breast.
• Stage 2 (T2): is a tumour between 2cm and 5cm across and breast cells are found in 1-3 lymph nodes in the armpit/near breastbone
• Stage 3 (T3): is a tumour greater than 5cm across, has invaded locally (into the chest cavity or skin) and breast cells are found in 4-9 lymph nodes in the armpit/near breastbone
• Stage 4 (T4) or advanced cancer: is a tumour which has spread systemically (into the brain, liver, bones etc.)

Other cancers like Colorectal Cancer use additional staging techniques for example Duke's Staging which is very like the numbered system but is marked by grade A-D. 

But the above is not the only way to identify the type of cancer! Oh no, like all aspects of cancer biology there is always more. 

While the stage/grade will help you with treatment options there are other factors such as location that tell you about the cancer.

For example in breast cancer:

Epithelial Tumours:

• Ductal carcinoma in situ (DCIS) - tumours in the ducts of the breast, non-invasive
• Lobular carcinoma in situ (LCIS) - tumours in the lobes of the breast, non-invasive
• Invasive ductal breast cancer - invasive cancer (invades into the basement membrane) originating in the ducts of the breast
• Invasive lobular breast cancer - invasive cancer (invades into the basement membrane) originating in the lobes of the breast

Other:

• Angiosarcoma of the breast - tumour arising from the lining of the blood vessels in the breast
• Paget's disease - cancer of the nipple

And as always we come back to DNA. There are mutations that are common in pretty much every cancer type (e.g. p53) but other mutations are specific to certain cancers of families of cancers. For example BRCA mutations are associated with both breast and ovarian cancers. 

In breast cancer the common mutations used to define cancer types are:

• Oestrogen receptor positive (ER+)
  • Luminal A - ER+, PR+ 
  • Luminal B - ER+, PR+/-
• Oestrogen receptor negative (ER-)
• Her2+
• Triple negative breast cancer (a collection of tumours with no mutations in ER, PR or Her2+)

In breast cancer if you have suspected Her2+ cancer a number of tests are done such as Immunohistochemistry (IHC) which detects Her2 receptor levels on the surface of the breast cancer cell and Fluorescence In Situ Hybridisation (FISH) which detects the number of copies of the HER2 gene there are.  

There are genetic screening tests used in the clinic for some cancers. In breast cancer there is OncotypeDx which detects 21 genes commonly mutated in breast cancer. This gives you a score. OncotypeDx also has systems for prostate and colon cancer.

Changes to the chromosomes themselves are also common, usually in haematological malignancies.

• Translocations: where one part of a chromosome switches with another part of the same or different chromosomes
• Deletions: where chunks of the chromosome are lost
• Duplications: where chunks of a chromosome double or triple or more

In chronic myelogenous leukaemia (CML), there is a translocation called BCR-ABL where part of the chromosome where the ABL gene is located (Chr.9) breaks off and switches with the part of the chromosome where BCR is located (Chr.22). This brings BCR and ABL together creating a powerful oncogene. 

And you combine them all. You take your image of the tumour(s) with all of the measurements and origin of the primary tumour, you get the pathologists report from the biopsy about the type of cancer it's believed to be, how fast it's growing, what proteins it may be expressing on the cell surface and how aggressive it is and lastly genetic testing to determine the mutations. This gives you a picture which allows you to provide the best treatment plan for that patient.  

So a patient could have a T2N1M0 ER+ invasive lobular breast carcinoma, meaning they have a breast cancer which originated from the epithelial cells in the lobes of the breast, the cells show structural changes and it is between 2cm and 5cm across, there 1-2 lymph nodes with infiltrating breast cells, there is no metastasis and the tumour is oestrogen receptor positive. The treatment path for this patient may be surgery to remove the tumour and lymph nodes involved or a full mastectomy. Depending on the surgery, the patient may receive chemotherapy and will more than likely be given tamoxifen (anti-oestrogen receptor drug) for 5-10 years. 

It's difficult to describe every type of cancer's staging systems because as I said it really is dependent on the type of tumour. ​

And that is the basics of it. As always if you have questions please don't hesitate to ask. This isn't all of the information and if you or someone you know is affected by cancer they should ask their attending physician to explain their diagnosis to them (cancer is so nuanced).

Hopefully in the next month or so I will put up our penultimate "What the Hell? - Cancer" blog post on Cancer Treatment!

For more information check out CRUK's website https://www.cancerresearchuk.org/​

I had a great time walking around Chiswick! It was fantastic to see the local community come out and run/walk against cancer. There were many stalls included CRUK science demos, face painting, a DJ from the local radio station, a burger van and more! The great volunteers and organisers put a massive effort into making the event fun and engaging! 

While the weather wasn't sublime it was perfect for running/walking in! The volunteers along the route were great at giving some encouragement, water and much needed directions! I was even given a jelly baby along the route which made my day! After 6km I was dying for some sugar! 

I love doing these volunteering events for CRUK, it gives me a lot of joy to be part of a team spreading such a positive message about beating cancer. And whether your event has 5 people or 5000 people, it can create so much awareness about cancer and about where money fundraised goes. I'm just glad to be a part of it! Even though I'm dying today after it! 

Just as an update, I did a little interview with the Chiswick Buzz at the end of the walk! If you want to see more about the day and also my small little part check out this link:

http://www.chiswickbuzz.net/community/chiswick-10k-fun-run-2017

​I'm at the end! 

On Thursday 1st June I was asked to present to a group of incredible volunteers for Cancer Research UK. Each year the Royal Family hosts garden parties at Buckingham Palace to show their appreciation for people who have made a positive impact in their community. It is a great honour to be invited. This year CRUK was allowed to send a small number of volunteers to the party to say thank you for being so great! I went to a pre-party gathering in the CRUK headquarters in Angel where I did a brief presentation about how I came to be in London, why I study cancer and the background to my project. 

It was a pleasure to meet these incredible women and to chat to them about my work! Please enjoy watching the video of my presentation. 

Warning: I say "em" A LOT! Also I exaggerated the number of women participating in the EPIC study - it's half a million.
Disclaimer: the opinions in this presentation are my own.
Thank you to Becky from CRUK for videoing this for me! 😊😊😊

Today I am starting a multiple part “What the Hell?” series on the subject of Cancer. There are many different aspects of cancer biology from what cancer is to how we diagnose and treat cancer and how we can prevent cancer. These posts will be a bit longer than usual so bear with me. I want to cover all of these subjects in enough detail that you as a reader can walk away with a few answers and maybe also a few questions.

HEALTH WARNING: These posts will be long. There is a lot of text. Feel free to read a little and come back.
 
To begin: If you don’t take anything away from these posts, I do want you to take away one VERY important thing. Like all facets of life, cancer is not black and white but a vast, daunting expanse of grey. As unique you are from the next person, cancer is unique to the person who has it. While cancers fall into “families” based on location or genetic similarities (e.g. breast, lung, etc.), each one has it’s own characteristics that make it unlike other cancers in the same “family”. In the simplest way I can come up with, cancer is a collection of your own cells that have gone mad. And that madness is unique to you.

Cancer classification
1. Solid Tumours:

• Carcinoma – originates from epithelial cells (cells that make up organs)
• Sarcoma – originates from supportive and connective tissue (e.g. bone, muscle etc.)
• Lymphoma – originates in the lymphatic glands and lymph nodes

Blood (liquid) Cancer:

• Leukaemia – originates from the bone marrow, cancer of the white blood cells made in the bone marrow
• Myeloma – originates from the bone marrow, cancer of the plasma cells in blood made in bone marrow

Terminology:

• Tumour: a mass of cells displaying uncontrollable growth and some/all of the “Hallmarks of Cancer”. Blood cancers are usually not called tumours because they don’t form masses like a solid tumour would.
• Oncogene: a gene consistently activated in cancer, which gives cancer a developmental advantage.
• Tumour Suppressor Gene: a gene consistently inactivated in cancer, which if activated would inhibit cancer development.
• Tumour Microenvironment: a tumour is not only made up of cancer cells but a number of other “normal” cells which have been hijacked by the cancer cells to produce a pro-cancer environment. These include stromal cells, immune cells and endothelial cells. ​

• Mutations: these are changes to the genetic code which suppresses gene expression or allows gene expression to be constantly active. 
• Genomic Instability: this is massive changes to the genome. Large sections of chromosomes can move to different chromosomes (translocation), a large section of the chromosome could be copied over an over or  a large section of a chromosome could be lost completely. 

​As I said cancer is your own cells that have gone mad. In more scientific terms, there a certain number of characteristics (or "Hallmarks") that define cancer set out by Hanahan and Weinberg originally in 2000 and later updated in 2011. Figure 1 shows the classic “Hallmarks of Cancer”. 

The first three Hallmarks are very related and focus around signalling. In a nutshell, cancer cells need to continue to grow while preventing the cancer cells from dying. 

(1) Sustaining proliferative signalling
Normal cells carefully balance growing with not growing. This process maintains the right number of functioning cells. Growth signals are given when more cells are needed but are shut off when no cells are needed.
In cancer, the growth signals are constantly active. This means the cells are constantly growing and dividing. They can do this in a few ways:

1. They make the growth signal themselves and use autocrine signalling to activate growth pathways without other cells.
2. They can send signals to normal cells in the tumour microenvironment to produce pro-tumour growth signals.
3. They can over-produce the receptor for the growth signal, making them hypersensitive to the signal (for example HER2). 
4. They can become growth signal independent by continuously turning on the pathways these growth signals activate (for example AKT/PI3K).
5. Preventing negative feedback. In normal cells when certain signals become too strong, this activates pathways, which dampen the signal. Cancer cells turn off these pathways.

(2) Evading growth suppressors
As I’ve said before growth is tightly regulated. There are lots of signals, which inhibit the growth of cells. Cancer cells actively prevent these signals from preventing growth. This can be done by:

1. Increasing signals that inhibit growth suppressors
2. Gaining mutations in key growth suppressing genes (known as tumour suppressor genes), which make them inactive.

The most commonly know tumour suppressors are p53 and Rb. As I’ve spoken about before in previous posts, p53 controls cell division. Similarly, Rb (first found to be a common tumour suppressor gene lost in Retinoblastoma) is a cell cycle check point protein. Cancer cells want their heavily mutated DNA to make it through cell division and these tumour suppressors would definitely prevent this. So they are prevented from working. 

(3) Resisting Cell Death
Cancer cells do not want to die. They want to keep growing and dividing. Normal cells have a few ways of dying which controls cell numbers but also prevents cells with DNA damage or bad mutations from becoming cancerous. These pathways include: apoptosis (programmed cell death), necrosis (un-programmed cell death) and autophagy (where the cells breaks down part of their own cell structure to survive). Cells receive internal (DNA damage, shortened telomeres etc.) or external signals (from other cells) which tell the cell "Listen...I think it's time for you to pop your clogs".
Cancer cells deregulate cell death pathways by shutting down the pathways that lead to cell death and increasing the pathways that inhibit cell death. This means no matter how many internal or external signals the cells get to die, the cancer cell will ignore them and continue being a cancer cell. 

In summary for the first three Hallmarks, cancer completely re-wires all the signalling pathways in the cell to promote their growth and division while ignoring any prompts to stop growing and die. 

The next three Hallmarks give cancer cells a growth advantage and allows the cells to move around the body. 

(4) Enabling replicative immortality
Cancer cells are immortal. This means if they were allowed to keep going uncontrolled, they will grow and never die. Normal cells have a life cycle. They grow and divide and if they don't receive premature death signals, they keep going until they have a "natural death". This is controlled by things called "telomeres". These are long stretches of "TTAGGG" base repeats that sit on the end of chromosomes, like the caps on the end of your shoe laces. They protect parts of the chromosome from being lost during cell division. Every time a normal cell divides the telomeres shorten a little bit. When they become too short the cell reaches a "crisis" and dies. This is a natural death for a cell. 
As a cancer cell starts to become malignant, the telomeres still shorten. However when the telomeres reach "crisis", the cancer cells turn on an enzyme called "telomerase". Instead of losing telomere repeats during every cell division, telomerase now adds telomere repeats. This essentially prevents the cells from going through natural death and makes them immortal. 

(5) Inducing angiogenesis
All your cells need a healthy blood supply. Blood vessels bring oxygen and nutrients to cells and take away all the bad rubbish like CO2 and waste. Your organs are covered in blood vessels to make sure every cell has access. When your cells have a good supply of oxygen it is called "normoxia" (basically normal oxygen). When your cells are starved of oxygen it is called "hypoxia".  You don't want your cells to become hypoxic because it kills cells. 
As a tumour develops it wants to grow near a good blood supply. But that may not be enough so cancer cells can grow their own blood vessels. This can be part of the early development of the tumour or because the tumour is so big the cells in the middle are all hypoxic. Cancer cells grow blood vessels by sending out messages to their local blood vessels (for example VEGF-A or FGF). This causes the blood vessel cells (endothelial cells) to branch off from the main blood vessel and grow towards the tumour. Tumour blood vessels are pretty badly made (figure 3). They're leaky and are pretty weak with large gaps between cells instead of a smooth blood vessel. While inefficient, they work well enough for the tumour to get the oxygen and nutrients it needs.

(6) Activating Invasion and Metastasis
The final established Hallmark of cancer is the ability of cancer cells to spread. 
​
Invasion:
Cells live together in organs and tissues. But there is a lot of stuff outside the cells which provide support and structure for the cells (for example collagen). This is called the "extracellular matrix (ECM)". The ECM is pretty stiff. This prevents cells from moving around too much, giving them an anchor to other cells. 
In cancer, cells want to occupy the area around them. Essentially they "invade" into the extracellular matrix. They do this by:

1. Firstly breaking down the ECM. They release proteins which chop up the rigid ECM structure, making it easier for cells to move around.
2. Secondly the cells transform into cells that are able to move. Epithelial cells (which are cells that make up the majority of organs e.g. skin) are unable to move around. However, mesenchymal cells (cells that usually make up connective tissues e.g muscle) are able to move. They use finger-like projections to drag themselves along. For a cancerous epithelial cell to move around in the ECM it transforms into a cancerous mesenchymal cell. This is called "Epithelial to Mesenchymal transition (EMT)". Once to cancer cells are transformed they can invade into the ECM, creating more space for the tumour to grow.  

Metastasis:
Invasion and angiogenesis (making blood vessels) allow cancer cells to metastasise. Metastasis is basically cancer cells moving from one part of the body to another. The primary tumour (the original tumour) forms a secondary tumour (the new tumour) in a different part of the body. The old tumour and new tumour share very similar characteristics. Cancer cells usually don't just move anywhere but pick specific parts of the body to call home based on the preferences of the primary tumour. For example Breast Cancer usually spreads into the chest cavity, liver and brain. How cancer cells pick the new sites is relatively unknown. 
Once the cancer cells invade into the ECM they can move towards blood vessels. When they're in the blood stream they surround themselves with immune cells. This is the not only to avoid being killed by the immune system but also to withstand the pressure of blood vessels. If the cancer cell did not protect itself it would be torn apart very quickly. The cancer cells can travel vast distances throughout the body. When a cancer cell picks a site for the secondary tumour, it leaves the blood and starts to break down the ECM at the new site to create space to grow. The cancer cells also transforms back into epithelial cells (MET). 
Even though primary tumours are constantly shedding cancer cells, only 0.1% of cancer cells broken off from a primary tumour actually form secondary cancers. ​

In 2011, Hanahan and Weinberg updated their Hallmarks with four more, two Emerging Hallmarks and two Enabling Hallmarks. 

Emerging Hallmarks
(1) Deregulating Cancer Energetics:
Cancer cells use a lot of energy compared to normal cells. This is because they are constantly growing and creating proteins, lipids and nucleic acids. The primary source of energy cancer cells use is glucose. To get the most bang for their buck cancer cells do something called the "Warburg Effect" (figure 6). In normal cells energy is made using "oxidative phosphorylation". While you get a lot of energy per glucose molecule, it takes a long time. Whereas another form of energy making,  "glycolysis", is extremely quick. You don't get as much energy but cancer cells are more concerned with speed than efficiency. Glucose can also run out quite quickly so cancers have adapted to use other sources of energy for example lactate. ​​

(2) Avoiding Immune Destruction:
Your immune system is pretty sensitive to foreign invaders. All cells have signals on their cell surfaces (called antigens). Immune cells produce antibodies which bind to these signals. If the signal comes from your own normal cells, the immune cell leaves it alone (kind of like a friendly handshake). If the immune system doesn't recognise the antigen then it attacks the cell. 
Cancer cells are not normal and do express antigens which immune cells do not recognise. To avoid being destroyed by immune cells, cancer cells express the "normal" antigens to trick the immune cells. Cancer cells can also hijack the immune system. By sending signals to certain immune cells they can transform them into pro-cancer immune cells. When an anti-cancer immune cell tries to destroy the cancer cell, the pro-cancer tumour cell comes in (kind of like a body guard) and suppresses the anti-cancer immune response.  
​

Enabling Hallmarks:
(1) Genome Instability and Mutation
I think I've established that cancer cells have lots of mutations which helps them grow and divide and generally be cancer. But there are certain mutations and genome instability events that are indicative of certain cancers. Cancers go though a transformation pathways from normal cells to malignant to metastasis. Each type of cancer has a sequence of events that gets them to that stage. For example figure 7 shows this sequence in Colorectal Cancer.

(2) Tumour-Promoting Inflammation
Inflammation occurs naturally in the body, usually in response to an injury. Inflammation is the response of the immune system to injury or damage. As I've said before, cancer cells hijack the immune system to protect themselves. But a side effect of this is the immune cells create a highly pro-cancer environment. Inflammation leads to the release of a wide range of growth signals, it promotes new blood vessels to grow amongst other things. In essence inflammation is the perfect environment for a tumour to grow. 

So those are the main Hallmarks of Cancer. While these were defined in 2000 and 2011, how cancer cells do any of these processes is still largely a mystery. I will talk later about how we can target Hallmarks of Cancer to kill cancer. 

Every year Imperial College London, UK hosts a science festival called Imperial festival. The festival boasts an impressive range of all different sciences from health to robotics and everything in between. 

Each year Cancer Research UK has a stand. This is because CRUK has set up research centres all over the country and one of these, based in Hammersmith Hospital, is the CRUK Imperial Centre. This is a collaboration between Imperial College London, Imperial College NHS Trust and CRUK to provide top notch support and facilities for cancer research. 

The stand was manned by enthusiastic researchers funded by CRUK and/or CRUK volunteers. Our job was to get the public enthusiastic about cancer research by joining in some demos. The demos included:

1. Smartphone microscopes - use the camera on your phone to see normal Vs lung tissue slides. 
2. Taste Test - There are receptors on your tongue which detect taste. The participant is given a small dose of PTC, which is bitter. If the gene for the receptor is unmutated (wild-type) then the person will get a really bitter taste. If the gene is mutated where only one copy of the gene is active, the person will taste a slightly bitter taste and if both copies of the gene are completely mutated the person won't taste anything. This doesn't mean any one of these people will get cancer but it is a good way of demonstrating intrinsic differences in all of us which are important when we study and treat cancer. 
3. Affinity & Beyond - When we treat cancer we want to ONLY kill the cancer cells. But a lot of treatments like chemotherapy can kill both healthy and cancer cells. By understanding the structure of the receptors for these drugs we can change the drugs to only bind to cancer cells, leaving the healthy cells unharmed. 
4. Conversation C - the general public are asked to take a seat with a researcher or two and discuss what they feel are the most important aspects of cancer research. They are then asked to distribute "resources" to each area. Topics: Lifestyle, Current Treatments, Diagnosis, What is Cancer, New Treatments and Genetics. 

I personally spent most of my time at the conversation C table. It was really interesting to see where people would put resources if they could choose. Surprisingly everyone started off with most of their resources in "Lifestyle". It makes sense, you want to prevent something from happening instead of trying to cure someone. But after a bit of discussion people started to move resources into "Genetics", "Diagnosis" and "Treatments". This was after realising that (1) people don't all follow the guidelines for a lifestyle that would reduce their cancer risk, (2) some cancers cannot be prevented by changing your lifestyle and (3) while this is a great long-term goal there are people suffering now who need short-term solutions. To my utter dismay, the most neglected topic was "What is Cancer?". To be able to tackle any of the other topics we need to know what we're up against. For example better understanding of cancer has lead us away from Chemotherapy and more towards personalised therapies. It was great to go and answer a few questions, have a chat and generally engage with the public. 

After participating in "Conversation C" I realised the most important aspect of cancer research to me is not any of the topics covered on the table. It was what we were doing at the table. Education and raising awareness of cancer can be such a powerful tool. As I said before, a lot of people don't change their lifestyle's even if they've been told it could reduce their cancer risk. From all the public engagement I have done with CRUK, plus this blog and chatting with people about my work, I realise that this is mostly down to the person not understanding why. Why does it increase or reduce my risk? What does risk actually mean? What is cancer? A lot of people don't even know certain things like obesity can increase your chance of getting cancer. For the cancers that still happen despite lifestyle factors, a lot of people don't know what genetic risk really means and don't realise the symptoms of a lot of cancers, which is why telling and engaging people is so important. 

I believe that if people were more informed and didn't feel like this was a subject you had to be a genius to understand (trust me I am far from being a genius) then you would have a lot more people willing to change their lifestyles or participate in studies and donate samples. This could change cancer research for the better. 

May is an interesting month in cancer awareness. Depending on the country you live it you are bringing awareness to Bladder Cancer, Brain Tumours or Skin Cancer/Sun Awareness. So to be fair I will do a little about all these cancers!

Bladder Cancer:
​
Bladder cancer is the 10th most common cancer diagnosed in the UK. Bladder cancer effects both men and women is more common in men compared women. Approximately 10,000 new patients are diagnosed every year and only 50% of those patients will survive 10-years or more. More than 50% of bladder cancer cases are diagnosed in patients 75+ years old. Over the last 20 years bladder cancer incidence has decreased by 38% with better diagnosis and treatments. As with most cancers, 42% of bladder cancer cases are preventable. 

There are two main symptoms of bladder cancer:

• Blood in the urine (4 in 5 bladder cancer patients will display this symptom)
• Problems passing urine - high frequency, urgency or pain

As with all "cancer related" symptoms these are not exclusive to cancer and could mean other issues. You should always go to your GP if you experience any of these symptoms. Bladder cancer is diagnosed by cystoscopy, urogram and biopsy.  The usual treatments are surgery (removal of the tumour or full removal of the bladder), chemotherapy or radiotherapy depending on the severeness of the cancer and how much it has spread. Unfortunately there are no screening measures currently available for bladder cancer.

Read more at:
http://www.cancerresearchuk.org/about-cancer/bladder-cancer

Brain Cancer:
​
​​Brain cancer (including other central nervous system and intracranial tumours) is the 9th most commonly diagnosed cancer in UK and effects both men and women. There are approximately 10,000 cases diagnosed every year however only 14% of those patients survive 10 years or more. Cancer is a disease commonly associated with ageing (older people are more likely to be diagnosed with cancer), however brain tumours effect people of all ages.  

As complicated as the brain is, the symptoms of brain cancer are numerous and equally complicated. For more detailed symptoms and information please visit CRUK's website: 
http://www.cancerresearchuk.org/about-cancer/brain-tumours/symptoms.
​Brain cancer is diagnosed using MRI, CT or blood tests. 

Brain cancer is one of the most difficult cancers to diagnose and treat. The brain is incredibly delicate and any damage could lead to long term problems. Usually when a cancer patient undergoes surgery, the surgeon tries to take a little of the "normal" tissue around the tumour. This area where tumour and normal tissue meet is called the "leading edge". This gives the surgeon more confidence that all of the tumour has been removed. But every single cell in brain in important. You cannot take big chunks of the brain out so surgeons must remove right on the leading edge. This sadly occasionally means some tumour gets left. Recurrence of the tumour is a lot higher in brain tumours compared to other cancers. Another issue with brain cancer is chemotherapy and radiotherapy. Chemotherapy does damage to normal cells, so giving a lot of chemotherapy directly to the brain is dangerous. Similarly radiotherapy can cause damage. They are incredibly difficult to treat and I have to commend all the brain cancer surgeons, doctors, nurses and care givers for their work. 

The positive it that there is a lot of research going into killing brain cancer cells without damaging the brain. One example is CRUK who have set up a funding initiative focusing on cancers with unmet needs, including brain cancer. So out there right now are researchers working on understanding, diagnosing and treating brain cancer.

Read more at:
http://www.cancerresearchuk.org/about-cancer/brain-tumours

Skin Cancer:

Skin cancer is the 5th most commonly diagnosed cancer in the UK with approximately 15,000 patients diagnosed every year. The positive - 90% of patients survive 10-years or more and about 80% of skin cancers can be prevented.  The majority of skin cancer is diagnosed in patients 60+ years. 

The common symptoms for skin cancer are:

• A spot or sore that doesn't heal within 4 weeks
• A sudden change in mole shape or colour (within weeks/months)
  • Asymmetrical moles
  • Lighter/darker colour in one part/all of the mole
• Red patches that don't heal within a few weeks 
• An ulcer on the skin 

Skin cancer is diagnosed by examination and biopsy. Skin cancer is treated commonly by surgery and chemotherapy. There is also a number of alternate therapies including a therapy called "Photodynamic Therapy" which uses a drug to make the cells very light sensitive and a light to destroy the cells (basically it causes so much damage the cells have to die). Imiquimod cream is also used which activates your immune system to destroy the cancer cells. There is no standard screening programme for skin cancer but you can be the most effective screening tool. By knowing your own skin and keeping an eye on any moles or red patches you should be able to tell when something is not right. This is when you go to your GP and get it checked. 

Here comes the sun awareness! There are two main UV radiation wavelengths that come from the sun and get through our atmosphere. The one most closely linked to cancer is UVA. UVA penetrates deep into your skin. When the UVA light goes into your skin cells it causes DNA damage. If the DNA damage persists through cell division (read: What the Hell? The Cell for more info) this causes cell instability and can lead to cancer. UVB tends to only penetrate the top layers of your skin, causing sunburn. To date there is no conclusive evidence linking UVB radiation to cancer. UVB actually stimulates your skin cells to produce vitamin D. But with one comes the other! And it doesn't matter if it is sunny or bucketing down, UV light still reaches your skin. While it is recommended that you spend some time outside every day, you need to take care of your skin with UVA protection. Your sun protection should have SPF AND UVA protection to be the most effective. Sun protection should be applied regularly. Wear a hat, avoid direct sunlight. If you don't believe me, ask Hugh Jackman!
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Read more at:
http://www.cancerresearchuk.org/about-cancer/skin-cancer

I wanted to give you a brief insight into some aspects of how cells work. This is a warm up for my next few blog posts about cancer. 

The Cell:
The cell is made up a whole lot of things (figure 1 shows just the bare minimum) which keep each cell and your body ticking over. Like a fried egg, the "yolk" of the cell is where all the genetic material is held. There are lots of things that want to degrade DNA in the "white" so DNA is kept in the "nucleus". RNA also spends some time in the nucleus and needs to be protected by "caps" on each end to stop it from damage (like a shoe lace). The "white" or "cytoplasm" is where everything else is. Mitochondria are the batteries for your cell. It is where all your energy is made. You have hundreds of mitochondria to power one tiny cell. Interestingly your mitochondria come completely from your mother. Ribosomes take the RNA made in transcription and translate this into a protein (see What the Hell? - Genetics for more detail).  The Endoplasmic Reticulum and Golgi Apparatus are important for the formation of lipids and some proteins and also modifying these proteins for specific functions (e.g. to sit in membranes etc.). The Cell Membrane is a double layered structure that maintains the cell's shape. It also controls very carefully what is allowed enter and exit the cell. For example, your cells need a constant balance of salts (sodium: Na+, potassium: K+ and chloride: Cl- also known as the membrane potential) to maintain ideal cell conditions. 

Cell Signalling:
Cell signalling is an incredibly important process for cell survival. It allows cells to communicate to each other as well as letting the cell respond to the external environment. Cell signalling is when a cell responds to a stimulus (either external or internal) leading to a biological process (such as cell division, transcription or cell death). Stimuli include hormones or proteins from other cells. 
Figure 2 shows external cell signalling in it's simplest form. Imagine you are playing catch with a baseball.  A ball (a stimuli known as a ligand) is thrown and is caught by a catcher mitt (known as a receptor). When the ball is caught it "binds" to the mitt. When the receptor on the outer surface of the cell binds to the ligand it sends signal the membrane into the cell. The signal is passed on, activating pathways as it goes or it can be sent back out of the cell. In normal cells, ligands bind specifically to certain receptors. For example oestrogen will bind to the oestrogen receptor.  

Figure 3 shows three types of cellular signalling:

1. Autocrine: The cell releases a signal which activates receptors on it's own cell surface
2. Paracrine: The cell releases a signal which is picked up by cells directly neighbouring it.
   
3. Endocrine: The cell releases signals which are picked up by cells very far away (e.g. different organs).

Back to our example if you played catch, an autocrine signal will be playing catch on your own, paracrine signalling would be playing with your team and endocrine signalling would be playing against another team from a different part of the city. In the end you can still play catch but with different outcomes (autocrine and paracrine are very local, endocrine is global). 

Cell Division:
Cell signalling can lead to a very important process in the cell - cell division. Figure 4 shows what happens in cell division. Cell division is crucial for cells to grow and maintain. Cell division allows two "daughter" cells are made from one "parent" cell. The daughter cells are identical to the "parent" cell and each other. This is known as mitosis. Cells are highly complex so duplicating the entire cell structure is a complicated business. Cells go through a number of checks during each "phase" of cell division. It works like a traffic light system, if you have the right conditions and pass all the checks (no bad DNA damage, no bad gene mutations etc.) the cell gets the green light. If there is damage or something like that, the cell gets a yellow until the problem can be fixed. If there is something very wrong or the problems can't be fixed the cell gets a red light. This drives the cell to die. This traffic light system occurs at every check point. Proteins control these check points and the most recognisable cell division check point protein (which you may already know and will definitely hear about A LOT) is p53. One of the things p53 checks for is DNA damage. If the DNA is damaged you do not want the cell dividing. Letting DNA damage pass can lead to DNA mutations or whole chunks of DNA being lost or moving about the genome. A lot of DNA damage can be repaired by a range of different methods but if it can't be repaired p53 pushes the cell to die.

Cell Death:
If there is irreversible damage to a cell, a process called apoptosis will be triggered. This process leads to the death of the cell. Figure 5 shows what happens in apoptosis. To begin, a stress signal is detected by the cell. This can be internal, like DNA damage, or external like sudden changes to the cell environment. Other cells can also signal cells to die. Once a death signal is detected this starts a cascade of signals that ultimately leads to the cell breaking up into fragments which are then taken up by neighbouring cells or excreted from the body. The number of cells in your body remain quite constant so when new cells are made, older cells die. This prevents DNA damage and bad mutations from persisting in the body. 

These are just a few processes in the cell which will help me explain what cancer is and how we can treat/prevent cancer. 

Keep an eye out in the coming weeks for "What the Hell? - Cancer".


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And just for fun I wanted to include what an actual signalling pathway looks like. Figure 6 shows the AMPK signalling pathway. AMPK regulates growth pathways and is commonly lost or down regulated in cancer. This, you will be shocked and appalled to know, is a pretty simple straight forward signalling pathway.

April is Bowel Cancer Awareness Month.

Bowel cancer is the 4th most commonly diagnosed cancer is the UK. Over 40,000 new cases are diagnosed every year but only 57% of these patients will survive more than 10 years. About 94% of patients diagnosed with bowel cancer are 50+ years old. It is a disease that effects both men and women. While the number of people diagnosed with bowel cancer has not changed in the last 20 years, the number of patients losing their lives to this disease has started to fall. This is due to better understanding of risk factors, better screening and better treatments. 

What is Bowel Cancer?
Bowel cancer is a disease that effects the "large bowel" which is made up of the colon and the rectum. This is why bowel cancer is commonly known as colorectal cancer. ​Bowel Cancer UK have a great interactive map on their website to explain what the large bowel is and how it works (https://www.bowelcanceruk.org.uk/about-bowel-cancer/the-bowel/). 

There are a number of symptoms for bowel cancer including:

• Bleeding from rectum and/or blood in your stool
• A change in bowel habit lasting three weeks or more
• Unexplained weight loss
• Extreme tiredness (with no reason)
• Pain or lump in the stomach area

Experiencing any of these symptoms over a prolonged period of time could be a sign of bowel cancer. However, if you are bleeding unexpectedly from anywhere I would definitely see a doctor straight away. 

How is Bowel Cancer Diagnosed?
If bowel cancer is suspected, the patient can undergo a number of exploratory tests such as colonoscopy. This allows a doctor to see inside your large bowel and identify any areas of trauma or if there are polyps present. Polyps are small growths in the lining of your bowel. They can be benign (no disease) or malignant (disease). If a doctor sees polyps he will take a sample (called a biopsy) for further testing. This biopsy is used to determine if there is cancer present and what stage the cancer is. 

How is Bowel Cancer Treated?
The most common treatments for bowel cancer are surgery, chemotherapy and radiotherapy. There are also more targeted therapies available for bowel cancer.

1. Surgery: degree of surgery can range from the removal of polyps and a small local resection to complete removal of the large bowel. This depends on the severity of the disease and how much it has spread. There is more detail on Bowel Cancer UK's website (https://www.bowelcanceruk.org.uk/about-bowel-cancer/treatment/surgery/types-of-surgery/).   
2. Chemotherapy: The patient is given a mixture of cancer damaging agents via IV over a prolonged period of time (weeks). Commonly chemotherapy agents for bowel cancer include: Fluorouracil, Capceitabine, Oxaliplatin and Irinotecan. 
3. Radiotherapy: low doses of radiation (usually x-ray) are directed at the affected area. This can either be external or internal (brachytherapy).
4. Targeted therapy: currently this is only available for advanced bowel cancer. These therapies specifically target bowel cancer cells. I will explain more about targeted therapies in an upcoming "What the Hell?" series. 

Bowel Cancer Screening:
Approximately 50% of bowel cancers can be prevented. With improved screening techniques, patients can be diagnosed earlier. In the UK there is screening programme in people aged 50 - 75 years. It is called the FOBT (Fecal Occult Blood Test). This test detects small amounts of blood in your stool. It is an "at home" test which you can do yourself three times over a two week period and send to a screening centre. If there is no blood detected you are ask to repeat the procedure in 2years time. If there is blood detected you are brought in for further tests. If no cancer is detected, the patient is placed on an observation programme to ensure the patient doesn't get cancer. If there is cancer detected, the patient in given further treatment. The FOBT test is slowly being replaced with a more reliable test called FIT (Fecal Immunochemical Test). This test detects the same thing as FOBT but there are far less false positives (blood when there isn't blood) and it is only done once, not three times over a two week period. If you have been sent one of these kits, please make sure you do the test. I now it's a bit gross but it could save your life. 


All the information for this post was provided by:
https://www.bowelcanceruk.org.uk/
http://www.cancerresearchuk.org/about-cancer/bowel-cancer

In today's blog post I am going to talk about something very personal. I am going to talk to you about what research can do to you physically and why you need to protect yourself.

The physical price I have had to pay has not been a pleasant one. Ignoring the constant exhaustion because you're stress dreaming every other night about a decimal place, I have recently been diagnosed with repetitive strain injury (RSI) in my right wrist.  For those that don't know me, my dominant hand is my right.  This makes basic every day things like washing my hair and dressing a constant struggle. You can imagine how well I can pipette or type.


What is RSI?
Repetitive strain injury (RSI) is an umbrella term for injury caused to tendons or muscles that experience constant use. There are many types of RSI including carpal tunnel syndrome and tendonitis. In fact I have tendonitis and tenosynovitis (i.e inflammation of two tendons in my wrist and thumb and inflammation of the muscle sheath that covers them). The pain can reach all the way up into my elbow and shoulder. I also have a good deal of muscle weakness in my right wrist, thumb and fingers. 

For more information about RSI: http://www.nhs.uk/Conditions/Repetitive-strain-injury/Pages/Diagnosis.aspx


What Happened?
I started developing pain in my hand in September 2016 but, as I do, I ignored it. It wasn't until I had an extremely important, sensitive experiment to do in November 2016 did my hand pain become a massive problem. I was unable to fully stretch my fingers or make a full fist. I had an almost claw hand. My knuckles were sore and I had pins and needles in my index finger (almost like it wasn't my own). Bending my wrist in any direction was agony. This, as you can imagine, made using pipettes incredibly difficult. Thankfully I work with some extraordinary people. The lab manager here, Nahal, also suffers with RSI and recognised the signs immediately. She pushed me to seek help and to stop working. She even helped me with the final stages of my big experiment (I had been building up to it for a year). I got to use a fully automated single arm machine which plated up my experiments for me. It was amazing! With Nahal's help, along with others in my lab (Annelie, Francesca, Ayse and Ebtihal), I managed to finish my experiment with pretty decent results.
Once I was done in the lab, I got help from the impeccable staff of the Occupational Health (OH) here in Imperial College London. They did assessments and in cooperation with my GP I had x-rays and blood tests. OH also provided physiotherapy to start me on the road to recovery. Thankfully I had a month at Christmas to rest my hand and (as you know) three weeks in France doing computer analysis to further rest my hand. I did go back to work after I came back from France, however I greatly reduced my lab hours to 1-2 hours per day, ONLY 5 days a week. 


What Caused my RSI?
Working too hard. I mean working myself hard. For 9 months during the first year of my PhD I worked 7 days a week, up to 50-70 hours a week. 90% of this time was in a lab constantly doing experiments (sometimes up to 6 or 7 a day, all at the same time). I actually calculated that I worked more weekend days in a four month period than I had taken off from January to September (including a two week holiday in September and Easter).  
I am a bit mad, I'm not going to lie. It has been not-so-subtly suggested more than once that I should seek mental health care. I don't really self-preserve. I push myself a lot. I need to be perfect and when I'm not I punish myself for my failure. When I'm not in work, I drive myself mad thinking about work (remember I mentioned stress dreams). This constant need to push myself effects my sleep patterns, eating patterns and my ability to feel and ignore pain. I have low grade chronic lower back pain from a traffic accident in 2009 but anyone looking at me would never guess.
I also have no ability to say "no". I have organised lab retreats, lab trips, charity events and raffles. I currently run the epigenetic unit meetings and manage (from a distance) the group journal club as well. As a CRUK funded researcher I have also said yes to (almost) everything CRUK have asked me to do. This means taking time off work to go to the PGA tour or half days to bucket collect etc. No matter what someone asks of me I will always say yes and give 1000%. And honestly, I love it. I love helping out, no matter what I'm asked to do. It gives me a sense of purpose, like I'm doing something right even if my lab work is going to hell. 
As I said I am a bit mad. But all of this has caught up to me and now my work and potentially my career is suffering for it. 


What is happening now (22/03/2017):
It is not going well. While the break and medication did reduce my pain and help me feel like I was getting back to normal, I was in fact kidding myself. My wrist muscles are pretty weak. I keep dropping things, which as you can imagine in a lab can be dangerous, and the pain is almost as bad as it was in November. Currently I am doing physiotherapy with the NHS. I am in a splint which does not let me move my thumb at all and I am doing strengthening exercises (I've even set alarms to remind myself). I am no longer in the lab. I am only doing computer analysis and that is pretty damn slow itself. Writing and typing is like being stabbed with tiny needles. I no longer work weekends (even on the computer). I have even been reduced to just cardio in the gym (I exercise 5-6 times a week because it calms me and makes me happy) which is INCREDIBLY BORING! All in all I am recovering but slowly. 


The moral of the story?
No matter what pressure you're under, no matter who puts that pressure on you, you need to protect yourself. My hand is my career. Without it I can no longer work in a lab. If I don't get over my own psychological issues and buck up I could be disabled for god only knows how long. This is WAY easier said than done. I am working on it. Part of the reason why I started this blog (you'll notice I started in November) is to alleviate some of the guilt I feel not working. 

For anyone who reads this who does lab or computer work PLEASE PLEASE PROTECT YOUR HANDS. I honestly mean it. I was you 6 months ago, not really paying attention to all those "ergonomic advice memos" and now I'm here, 6 months on struggling to wash my hair because my hand hurts so much. You do NOT want to be me! Thankfully I have become a bit of an example in my group and people are paying more attention to their working practice. I have brand new ergonomic pipettes (THANKS JAMES!!) and a new look on my working life. I will never have a relaxed attitude about working and being the best but I am definitely going to take my time from now on. 

I hope my hand does get better and I can get back some of my life 6 months ago (not all of it, weekends will have to become work free zones). 

I will keep you updated on how my recovery is going. 

I wanted to write a quick post to acknowledge something I think is pretty great! I was recently (and by recently I mean this morning) included on the European Association for Cancer Research (EACR) fortnightly member's email bulletin!!! It's a big deal for me because it gives me hope that what I'm writing here isn't completely inept!

I want to say thank you to EACR for believing that my little blog is worth publicising and hopefully I can make them proud!