The staff and the organisers of the event were brilliant and so accommodating. They have this wonderful sort of art installation where the public/researchers at the Crick ask "What...the one thing [they] would like to know about the human body, how disease develops or how they might be treated?" I found one I thought was very insightful from a 17 year old, "Do atoms have motives?".
The first day opened with two key note speeches from two extraordinary researchers.
The first speaker, Dr Lewis Cantley, discovered the PI3K signalling pathway (which is a big deal trust me, this is one of the biggest signalling pathways there is and it is incredibly important in cancer biology). He actually spoke about something very close to my own research. Insulin resistance (hyperinsulinemia) is a risk factor for many types of cancers. The liver, skeletal muscle etc. become resistant to insulin signalling, leading to a build up of insulin in the blood. BUT cancer cells are highly sensitive to insulin, meaning this high blood insulin environment is perfect for the cancer to grow in. Insulin itself activates pathways to make cells grow and divide. PI3K is part of the insulin signalling pathway. Dr Cantley talked about how using PI3K inhibitors (which are already being used but can become ineffective) in combination with a modified diet could help enhance PI3K inhibition for cancer treatment. And funnily enough this PI3K and metabolism subject came up a lot throughout the two and a half days, not just in the "Metabolism" session.
The second speaker was Dr. Lisa Coussens, who is a big name in cancer immune biology. Dr. Coussens spoke about the immune cells in the tumour microenvironment and how this can contribute to inflammation around tumour cells. She also spoke about how immune cell infiltration into tissue can contribute to tumour development and metastasis. Understanding the different immune cell infiltrates will help is understanding tumour development and also potential treatment.
The second day was long, very long (11 hours from arriving to leaving). The day was packed with talks and poster presentations. I won't go through every single speaker's work in detail but I will highlight some areas I found particularly interesting. My main reason for attending this conference was the session on metabolism. I have five pages of small scribbled notes in my notebook from the five talks compared to one or two for the other sessions. Not the other sessions weren't interesting. Unfortunately I can't really discuss a huge amount of what was talked about because most of the data is unpublished and you have a professional courtesy not to disclose the information.
Session 1: Metabolsim
This session really focused on how understanding metabolic processes, the metabolites that are used in these processes and the metabolites derived from those processes could help in not only understanding how tumours are formed but also how was can target these tumours as individual treatments themselves or in fact enhance current treatments. As I've said before it's been shown that different diets can enhance the effect of anti-cancer drugs.
Session 2: Tumour Microenvironment
I've talked about the tumour microenvironment (TME) before in my "What the hell? - Cancer Part 1" post. The TME is made up of a number of different cell types (immune cells, blood vessel cells etc.) which all contribute to the development, growth and spread of cancer. In this session we discussed how we can understand the interaction between the cells in the TME and cancer cells. Mainly this session focused on infiltrating immune cells (immunology is a hot topic now so it came up in pretty much every talk at some point....) but there was one talk which was very interesting about identifying mutational signatures in breast cancer that can identify the type of cancer it is, can put together cancers that may not look the same but have similar mutations and can tell you about potential treatment pathways (Serena Nik-Zainal).
Session 3: Tumour Immune system interactions
As I said immunology in cancer is a hot topic in recent years. This session focused on targeting immune cells to kill cancer. Immune cells can be pro tumour and anti-tumour depending on the signals it received. Cancer cells can send out signals that activate immune cells that dampen down the immune response while also pretending they're normal cells to immune cells that would kill them. Immune cell infiltration into the tumour can happen at different stages of tumour development and the context (I learnt) is pretty important for choosing what cells to inhibit to kill cancer cells. Interestingly the metabolism/immunology sessions combined for a talk by Luke O'Neill (a lecturer in Trinity College Dublin). While by far the most entertaining lecture he also made an interesting point about how different metabolites can be pro-inflammation or anti-inflammation. While he doesn't focus on cancer, he made the interesting point that targeting immune cells could be again achieved or enhanced by looking at the metabolism of the cell you're targeting.
Session 4: Tumour heterogeneity and evolution
The final session was a mixture in terms of biology and statistics. We had talks about cancer evolution, specifically the evolution of drug resistance (drug resistance is a big problem in all cancers) and heterogeneity of cancers. If we can understand how drug resistance occurs we could target cancer cells better so it doesn't happen. A lot of that has to with the fact that tumours can have multiple cancer cell sub-groups which have different mutations (heterogeneity). The statistics talk was interesting but I was very much out of my depth. What really fascinated me and kind of scared me was the talk on brain tumours. Basically brain tumours act like mini-brains. They form cell-to-cell connections through micro-tubules. This tubes allow the cell mass to become more resilient to therapy (e.g. radiation) and also allow repair of damaged parts of the cell network (which brains do not do). Frank Winkler showed videos of the brain tumour cells and even compared them to normal brain cell connections. While scary to know, this is brilliant for brain tumour biology and treatment. Recurrence is common in brain tumours and these tubules could help give an answer as to why. And they could be something that can be targeted. More work needs to be done but that talk was brilliant.
I first want to explain what a poster session is for those who don't know. Basically you submit a short description of your work and if you're chosen you create a poster (A2) to demonstrate what your work. The more figures the better. You then have an opportunity to stand beside the poster and chat to any interested person who comes along. I want to thank the people who happily stood and answered my weird questions about their work. You're very patient humans. I want to say I went and talked to everyone about their posters (there were 74 by the way) but I hunted out the epigenetics posters and ones that really interested me. I chatted with Tim Fenton from UCL, James Heward from Barts and Neil Slaven from Imperial. I can't really tell you what we talked about because their work is unpublished but needless to say it was very interesting.
All I all it was a really interesting conference, if not a a small bit tiring. My only problem with the conference as a whole was the very small representation from the area of epigenetics. Some speakers mentioned epigenetics (one even had a little data) and there were a few posters on the subject but it was distinctly lacking. I know that's the area I'm in so I am very biased and obviously it was hard enough to fit all the talks they had already into the two and a half day schedule, but it was missed. It may not be the area that solves all the problems (my PhD title will of course be "I cured cancer with epigenetics, everyone can go home now") but it provides a key piece in the puzzle. It's something I hope the organisers will consider for the next Crick International Cancer Conference.
Other than that the 1st Crick International Cancer Conference was worth attending and I learnt some interesting (and terrifying) stuff.
You may (or may not) have noticed that my blog has been all but quiet and desolate the last three months. This is completely my fault and an unconscious act of neglect. There are two main reasons why I have been so absent and hopefully I can give you many excuses to explain these reasons while also updating you on my progress.
The first reason is work. In mid-August I had what's known here as a Late Stage Review (LSR). This is something all Imperial PhD students are required to do in order to complete their PhD. The aim is to present your results and future plans after around 2 years of doing your PhD. You make up a report and do a presentation for two examiners. They judge your work and your ability to complete your PhD and sign you off. Usually they don't fail people (there is always the possibility) and the idea is for them to give you ideas for finishing your thesis and focusing your work. Obviously you want to present as much good data as possible. Hence the absence beforehand. I spent all my time writing the report and generating as much data as I could. All in all the LSR went fine. My work is satisfactory enough to continue. However I am not going to lie I was disappointed afterwards. I thought going in that they would help me narrow down and focus on the more important aspects of my project but instead I was told to "expand more to focus more". I realistically have 12 months left in the lab. This was not what I wanted to hear. I need to add more work to quite frankly an already daunting amount of work. Following from that I wanted to finish up at least one part of my project (validating my significant probes found from the DNA methylation array in another format i.e pyrosequencing). And this you will be happy to know showed...........nothing. Bupkis. Nada. I have negative results. While this is not an epic failure (as my brain wants me to believe) nor is it a triumph. Essentially what this means is I need to go back to my plan and look at the question a different way. And this is when I appreciated the LSR. Yes I needed to do more work but actually it gave me an opportunity to approach my project at a slightly different angle and who knows maybe something will work. I am now in the stages of planning and implementing that work. And who knows maybe in a few months time I will have something positive to talk about.
The other reason I have been absent is I went on a 17 day holiday. I travelled to Rome, Sicily, Dublin and Cork. It was amazing and relaxing. And I didn't have to worry about my project or stress about what I needed to do next. I even slept the whole way through a night for the first time in, well, years. It was incredible and for anyone looking for their next holiday destination I highly recommend Sicily. Get a car like we did, drive around and soak it all in. Mountains, crystal clear water, food. A must really.
And finally on a slightly different note I am taking up some teaching! An ex-member of our lab, Kirsty, is part of a team which has created a brand new innovative BSc undergraduate programme in Imperial. The course focuses on interactive learning and face-to-face teaching. It will be one of the first courses of its kind and hopefully not the last. Part of this course is to teach laboratory skills, called lab pods. I will basically be a part of a team of PhD students in these lab pods who will help guide students through techniques like cell culture and western blotting. Guide being the operative word. Unlike traditional teaching labs where I would show them what to do and answer all of their questions for them, this lab aims to make scientists. So I am really there to watch and provide last resort help. The idea is that the students will get a protocol, read through it and do the experiment. If it goes wrong then they have to figure out why. Exactly like anyone working in a lab would. Besides having a master student, I haven't really taught before so this is a new and exciting experience! Terrifying (especially when you realise you're about 10 years older than they are) but exciting.
And that's what I've been doing. hopefully I will be a bit more dedicated to the blog and I can keep you updated on my work, my teaching experience and also complete a few posts (such as my "What the Hell? - Cancer" series).
Btw I am not quitting this PhD any time soon in case you were worried.
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.
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...
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.
The next three are characteristic of pre-cancer cells (i.e. structural changes that can lead to cancer):
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.
Staging and Grading
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.
Clinicians expand on this and use a system called TNM. This is "Tumour", "Node", "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:
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:
Mutations and Chromosomal Changes
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:
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.
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/
On Sunday the 25th June I participated in the Chiswick 10K Fun Run! I am not much of a runner but I did walk very briskly! I also had the great opportunity to say a few brief words before the event to thank all the participants and tell them where their hard earned fundraising goes.
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:
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.
1. Solid Tumours:
Blood (liquid) Cancer:
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:
(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:
(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.
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:
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.
Figure 4: Tumours release signals into the microenvironment to create a path for an individual cancer cell (purple cell) to get to blood vessels. Once in the blood vessel, the cancer cell hijacks immune cells to protect itself (blue triangles). The cancer cell can travel vast distances all around the body. The cancer cell then leaves the blood vessel. It breaks down the microenvironment around itself to create a space to grow into a new tumour.
In 2011, Hanahan and Weinberg updated their Hallmarks with four more, two Emerging Hallmarks and two Enabling 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.
(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:
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 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:
Read more at:
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:
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.
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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:
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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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 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 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:
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.
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".
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:
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.
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:
My name is Caitriona and I am a PhD student at Imperial College London, UK.