Your guide to understanding cancer

In order to understand this story, I need to take you way, way back; in fact so far back that time hadn't even begun. Well it had for the World of course, but not for this particular human being a human we're going to call 'You'.
It all starts one romantic evening; it was cold outside, but inside conditions were perfect, enabling the coming togetherof a sperm (donated by You's father) and an egg (donated by You's mother). This was one of the most miraculous and important events in humankind, as by the joining together of this sperm and this egg (both cells in their own right) a beautiful new cell was borne, a new cell that would grow up to become You. 

Now, before the story can continue, I want to take you on a breathtaking journey deep intothe centre of a cell…
 
Small but Beautiful
Miniscule it might be, but the cell is an incredible and complex 'factory', somewhat self-contained and self-maintaining: it can take in nutrients, convert these nutrients into energy, carry out specialised functions, and reproduce as necessary. And each cell has its own set of instructions for carrying out each of these activities.

Let's begin by gently penetrating the Cell's protective, plasma membrane – amongst the proteins and lipids (fat-like molecules) you'll notice a variety of other molecules that act as channels and pumps, moving different molecules into and out of the Cell. Now we enter the Cell's inner space – the cytoplasm. As you can see, it's a salty, jelly-like soup, and as we make our way through it, you'll notice it's full of organelles. These are like mini organs, and each one has its own name and function. For example that one there is a ribosome, which is responsible for producing proteins. Protein synthesis is extremely important to all cells, and therefore a large number of ribosomes – sometimes hundreds or even thousands – can be found throughout a cell. And over there are a couple of the Cell's power generators called mitochondria; and now we're passing the waste disposal units, or lysosomes and peroxisomes. Lysosomes are pretty cool – one function they have is to digest foreign bacteria that invade our Cell. They also help recycle receptor proteins and other membrane components as well as degrading worn out organelles such as mitochondria. Lysosomes can even help repair damage to the plasma membrane by serving as a membrane patch, sealing the wound!

But it's the next organelle that I really want you to see. We're now approaching the very centre of the cell, and there it is – that spheroid-shaped thing is called the nucleus – it's the Cell's control centre. Inside you'll find chromosomes, responsible for storing the Cell's entire identity, or DNA. Combinations of this DNA form Genes, which are the instructions on how to 'build' this particular new person eg what colour eyes they will have, how tall they will grow, etc. We can't enter because security's tight – in fact it's separated from the cytoplasm by a membrane called the nuclear envelope. This isolates and protects the DNA from accidental damage caused by negligent molecules, and stops those other busy-body molecules interfering with all the complex processes which are happening in there.

So, now you realise what complex, little structures cells are, we can move up and out and on with the story.
Go Forth and Multiply
Let's go back to that miraculous new cell that was created when the sperm and the egg joined together. What happened next is just as amazing…

First, the chromosomes in the nucleus lined up in an orderly fashion right in the centre of the cell; they then split into two identical halves, the cell 'folded' in the middle and suddenly split in two. One cell had become two, both exact copies of each other! Then it happened again, and this time both cells divided creating four identical cells… and then all four divided creating eight cells… and the eight cells became 16 cells… and on and on they continued dividing. Each cell was identical, and each cell contained a full set of chromosomes, or instructions on how to build You.


Stem Cells
At this stage, the cells had no clear idea of what role they would play in the building of You – which of them would become skin? Or liver? Or blood? They were like eager students waiting to find out in which subject they would specialise! They were therefore called 'Stem Cells' (as all future specialist cells will have stemmed from them). It wasn't long however, before the 'Professor' – a biochemical – appeared, and these Stem Cells were given their new roles. This defining moment in each cell's life is called differentiation – each cell has some of its genes 'turned on', or activated, and others switched off, or inactivated. This process was intricately regulated, and as a result, each differentiated cell went on to develop specific structures and perform certain functions, resulting in over 200 different types of cell. Once each cell had been given its 'career' path, its descendants would all follow in its 'footsteps'. For example, once a cell had taken on the role of a skin cell, it would only be able to reproduce more skin cells, who in turn would only be able to produce skin cells, etc. (Unlike many of the other roles, eg liver cells, there were some options open to skin cells, such as what type of skin cells they might become; this was the same for cells in the bone marrow that could go on to become platelets, white blood cells or red blood cells.)

To Grow or Not to Grow
As you can imagine, the speed at which the different cells continued to duplicate, had to be extremely carefully orchestrated, otherwise You would've ended up all over the place! Each cell, therefore, received strict instructions via Growth Factors, as to when it should divide. Thus, working in harmony, the cells continued dividing and the body continued growing; finally You was born; You then became a toddler, then a teenager and finally, You became an adult. There were now approximately 100,000,000,000,000 cells making up You's body – that's an awful lot of cell division. And an awful lot of chances for things to have gone wrong! But don't worry, a highly sophisticated surveillance system had been set up to monitor each cell as it divided, to see if any damage had been caused to its DNA; it was also able to spot if a cell was failing to perform critical processes. If the system sensed a problem, a network of signalling molecules instructed the cell to stop dividing. These so-called 'checkpoints' then let the cell know whether to repair the damage or initiate 'programmed cell death' – cell suicide! This may sound drastic, but programmed cell death was the only way to ensure that the damaged cell could no longer reproduce. (Scientists know that a certain protein, called p53, acts to accept signals provoked by DNA damage. It responds by stimulating the production of inhibitory proteins that then halt DNA replication.) Once an adult, most of You's cells stopped dividing, and concentrated on the job they were required to do, as that particular part of the body. They only reproduced in order to replace other cells that had died, or if they needed to repair a wound. For example skin cells were constantly shedding and being replaced. Those cells that did carry on reproducing included sperm cells, hair cells, cells in the gut and cells that make blood in the bone marrow. Some of the other cells actually lost the ability to reproduce; but not to worry, because there was always a sufficient supply of immature stem cells, which could have their genes switched on or off in order to be turned into the required specialised cells to replace cells that had been damaged or killed. So, for the following 40 years or so, You continued to live a mainly happy life. But then one day, You noticed something unusual – a lump…

Why? How? When?
And this is where the story gets a little scary. What on earth was this lump? How had it developed? How long had it been there? Don't get me wrong, there had been many 'lumps' in the past, but they had always been soft, squidgy, friendly, fatty lumps or cysts. This lump was different. This lump was hard. Now, in order to find out what was going on, we needed to take another journey, this time into the body, in order to get a good look at this 'lump'… And, just as suspected… for some unknown reason, some of You's cells were out of control. Something must have damaged a single cell's DNA or disrupted its metabolic processes and instead of doing the right thing and initiating programmed cell death, it had evaded or ignored the surveillance and signalling systems, and started duplicating. Each 'offspring' received a copy of the 'bad' DNA, and hence they too went against the laws that regulate normal cells, and continued to divide uncontrollably. In a way, they had become 'immortal'. As a result, a tumour had formed made up of billions of copies of the original cancer cell – and this was the hard lump You could feel.

Who's the Culprit?
This is a difficult question to answer. Most baddies become known to the police – or in this case scientists – sooner or later. And some of the best known are the carcinogens. These are nasty, cancer-causing agents; sadly, it's almost impossible to avoid them – they might be a chemical, a virus, radiation or even a solid material. Once a carcinogen (radiation, pesticide, tobacco smoke, etc...) enters the tissue it is broken down into an unstable molecule. These chemically unstable molecules then become known as Free Radicals. Free Radicals attack stable molecules, 'stealing' their electrons. When the 'attacked' molecule loses its electron, it becomes a Free Radical itself, beginning a chain reaction. Once the process is started, it can cascade, finally resulting in the disruption of a cell. Also, although the cells have developed incredible mechanisms to compensate for these carcinogens, there is a limit to the amount of exposure they can take. If they are exposed to too many, they can become 'overloaded with Free Radicals'. Or perhaps it was just an accident? Perhaps over the many years of life, some genes became damaged or lost, genes that were meant to be 'switched on' remained permanently 'switched off ' and eventually cells were formed that no longer responded to the signals. Or perhaps there was a faulty gene right from the start. We just don't know.


Digging Deeper
What we did need to know, however, was how aggressive this tumour was. Unlike reproduce the less specialised they become. And as they start to lose genetic material they become more primitive and tend to start reproducing more quickly and more haphazardly. So, when rating a tumour, we need to look at how normal the cells appear in order to see how advanced it is. We can then grade the tumour between one and three – three being the most aggressive.

Malignant or Benign?
Now for the critical stage. If it's a benign tumour, then although it will continue to grow, that's all it will do. It might push other organs out of the way, but it won't invade them, and it will never spread to another part of the body. Benign tumours are generally non life-threatening, as they can be completely removed by surgery (except for those that occur in inoperable places such as some brain tumours). However, if it's malignant not only will it continue to grow, but it will flout other laws which control normal cells. It will be capable of invading adjacent tissue, and of spreading to other tissues and organs (this is called 'metastases' - 'meta' means change and stases means places). This tumour will now be referred to as 'cancer'. Its first move will be to invade underlying connective tissue, before continuing to multiply and spread through the normal tissue surrounding the primary tumour. It might then spread directly into other organs eg colon cancer can penetrate the walls of the colon and invade neighbouring organs such as the bladder or small intestine. Having invaded the normal tissue surrounding the original site, the cancer cells can then burrow through the wall of a blood vessel to get into the blood stream. Once inside 
this circulatory system they are swept along and can be carried to any site in the body. However, it's quite a turbulent journey, and they get battered around by the fast flowing blood; the cells must also escape recognition and destruction by the immune system, before attaching to, and then penetrating, the walls of smaller blood vessels, called capillaries, where they can initiate new growth. The cells usually stop at the first place they become stuck, which is often the nearest organ. The new growth is called the 'secondary cancer' or 'metastasis'. Another way they can get around the body is via the lymphatic system. The lymphatic system consists of organs, ducts, and nodes. It transports a watery, clear fluid called lymph. As with the blood network the lymph vessels form a network throughout the body. Lymphocytes, the principal cells of the immune system are also carried through the body in the lymphatic fluid, and hence the lymphatic system plays a major role in the body's fight again diseases. It appears that lymphocytes can recognise and destroy some cancer cells, but others escape undetected. The extent to which a tumour has spread is frequently estimated by examining lymph nodes in the area of the tumour for the presence of cancer cells. 

The Cure for Cancer 
As you know, normal cells are confined to their site of origin; however, should they for some reason 'wonder' to another part of the body, they will automatically self destruct. However, cancer cells don't obey this rule, and it's this trait that is responsible for most cancer deaths. If the cancer is reached whilst still in situ, then it can be completely removed by surgery. Hence the quicker a cancer is found the better. However, once it has started invading the surrounding normal tissue, the effectiveness of the surgery depends on removing all of the tissue that contains cancer cells. And as soon as it has spread to other parts of the body, then a multiple attack may be required involving surgery, chemotherapy and radiotherapy Surgery and radiotherapy are good for attacking the primary site of the cancer. But if the disease has metastasised then chemotherapy or hormones that can permeate right round the body are needed. If these drugs can kill the cancer cells then cure can be achieved – the abnormal cells can run but they have no place to hide. 

The Good News 
The good news is that cancer treatment is getting better all the time. Nearly 50 per cent of all patients will be completely cured by modern treatment. Surgery and radiotherapy are getting far more sophisticated at targeting cancers much more precisely. And we are in the middle of a real molecular revolution to understand what makes cancer cells tick, and destroy them effectively by new targeted drugs. The future is extremely promising. Personalised treatment plans using amazing imaging techniques to map out the exact site of the primary cancer create new opportunities for keyhole surgery and precision radiotherapy - more effective but less destructive. And new diagnostics that look at the cancer cells from a patient to find out why things have gone wrong will allow personalised programmes of effective drugs to be devised. We may always face a war against cancer, but there may come a day when we win every battle.