The cancer crab

It can take many years for a damaged cell to divide, grow and form a tumour big enough to cause symptoms or show up on a scan. Prof Carol-Ann Benn helps us understand just how this cancer crab creeps in.

---

I’m often asked why there is so much cancer today, and to be honest most of us pseudoscientists have many theories but few answers. 

So, let’s understand the terms and what happens at a cell level.

Cancer is the Latin word for crab or creeping ulcer. Hippocrates, The Father of Medicine, is said to have named masses of cancerous cells Karkinos. This is Greek, not Latin. Could they have got this meaning from the stars? 

Cancer, like crabs along the rivers scurry in a non-systematic fashion. Could this be the result of them popping up from little burrows, suddenly seen, or because of their hard shells and protective carapaces, resulting in difficulty in treating them, or possibly the crab-like tendency of a malignant tissue to grasp the tissue it invades. Actually, the swollen veins around the tumour resembled the limbs of a crab. 

The first paper about canker (old word for cancer) dates back to 3000 BC and is called the Edwin Smith papyrus and describes eight cases of tumours of the breast that were treated by a fire drill; with, let’s be honest, zero success.

How does a cancer crab start?

It’s an abnormal cell line (all cancers begin in cells) that starts to develop and grow out of control. 

Now remember we have billions of cells in our body, and cancers start by a small change in one cell or a small group of cells. Cells aren’t like people that sometimes don’t obey the rules. They always follow the rules.

We have the correct number of cells and they all produce signals to control how they behave, when they divide and how often. All cells have different jobs, but they’re similar in how they’re composed. They have a brain or control centre, called the nucleus. Inside the nucleus are chromosomes made up of thousands of genes. The genes contain long strands of deoxyribonucleic acid (DNA) that codes messages, telling the cells how to behave. The gene is an instruction manual telling the cell to make something. This could be a protein, or a different type of molecule, called ribonucleic acid (RNA). Together these proteins and RNA control the cell and decide what type of cell it will be, what it does, when it divides and when it dies. The genes ensure that the cell grows and reproduces in an orderly and controlled fashion. This is what keeps the body healthy.

So, why would cells decide to go AWOL and not listen to the big daddy pluripotent (original cell line)? Well in all families, remember there is that one, and sometimes if the signals are faulty or missing, much like that completely delinquent child, they grow. A combination of genetics and environmental factors results in the stars aligning themselves in that stripe and so a non-star/monster is born. 

Mutations

When a change happens in a gene and the cell divides, it’s called a mutation. This means that the gene has either been damaged, lost or copied too many times. Mutations can happen by sheer chance or by environmental and genetic factors. Sometimes when mutations happen, the cell no longer understands the instructions given to it and will grow out of control. 

There needs to be at least six different mutations for a normal cell to turn into a cancer cell, and according to the Cancer Genome Project at least 60 mutations are seen in each cancer cell. 

Mutations in genes result in cells making too many proteins that cause a cell to divide, or the cell stops making proteins that tell it to stop dividing, causing abnormal proteins to influence the cells behaviour. 

Genetic changes can occur if you inherit them from your parents. The inherited gene is in either the egg or sperm at conception and lands up in every cell.

Mutations can happen by chance when a cell is dividing. They can also be caused by the processes of life inside the cell, such as the cell getting older, or by a failure in the cells genetic blueprint. 

Environmental factors, such as tobacco, alcohol, toxins as well as toxins produced in our body fat all contribute to the development of cancer.

Some genes get damaged every day and cells are very good at repairing them. But over time, the damage may build up, such as sun damage. And once cells start growing too fast, they’re more likely to pick up further mutations and less likely to be able to repair the damaged genes. This is why we see more cancers in older people.

We all have abnormal cells

This is where the concept that we all have cancer cells comes in. Actually, we all have abnormal cells, but our bodies have ways and means and clever SWAT teams to rectify them. Clever security systems exist yet cancer cells can still evade our policing systems. They slip past our body’s internal protections by developing disguises (mutations).

Where the mutations happen in the cells help the cancer cells survive. These may happen in tumour suppressor genes; these genes ensure cells divide and die at the right time as well as fixing DNA mistakes. 

Because of the genetic mutations in cancer cells, they keep dividing and ignore the body’s signals to stop dividing. Our bodies have a very clever built-in process, called apoptosis or programmed cell death, that is like a red button (like in all the movies) for cells it doesn’t need anymore. Normal cells listen to the body’s cues and stop reproducing when told enough is enough. 

Because cancer cells are growing fast, they don’t go through the usual cell development phases, and don’t mature and become the grown-up cells they are supposed to be (they remain insolent and delinquent teenagers). 

Normal cells mature into distinct types with specific functions. Cancer cells can therefore influence normal cells and affect their behaviour, such as recruit them to develop blood vessels to keep the cancer alive and thus help provide the cancer cells with oxygen and nutrients. See we all need to watch the company we keep. Cancer cells like, all good criminals, trick our immune system. 

Our immune system is the police force that fights infection and disease and gets rid of abnormal and damaged cells. So, you could say cancer cells bribe the police cells. Because cancer cells ignore the body’s signals to stop dividing, they invade nearby tissues.

Eureka opportunity 

Cancer cells take years to develop; this process of multiple changes is called the microevolutionary process of cancer development. Because there are so many mutations present in these cells (some have nothing to do with the actual cancer’s ability to grow), looking for a quick fix, on-off button, one single treatment for cancer is like looking for a needle in a haystack. 

Therefore, when a practitioner offers a single herb medicine substance to cure all cancers, this isn’t possible. Added to this, different cancers will have different mutation signatures. However, certain genes are seen more frequently in all cancers and this eureka opportunity has provided our clever pathologists and scientists the ability to develop treatments for these proteins or receptors. 

Examples of these are the genes for the signalling protein Ras (sounds like the all-powerful sun god) that is a growth-promoting gene; by stimulating growth factors you naturally promote cancer cells to grow. 

A receptor that is often seen on cancer cells is the tyrosine kinase receptor and a drug many of you will know is trastuzumab which blocks this overactive receptor.

Some cancer mutations affect the brakes on cells. Genes known as tumour suppressor genes act as brakes on cells that want to divide uncontrollably. Our bodies are so clever; there are two brakes like a bicycle. And cancer genes need to have and often do have two mutant copies of these genes (an example is the p53 protein), thus switching off the brakes for proteins that sense DNA damage.

All these findings of how cancer cells work provides the scientist with options for developing a multitude of clever drugs that work specifically against cancer mutations.

The downside – cost

Sadly, the development of these drugs is hugely expensive. Always check that you’re being treated in a multi-disciplinary accredited unit that has access to trials and research as this is often a way to improve access to these new fancy treatments.

How do we catch the cancer crab?

Doctors use various techniques for finding cancer cells: blood tests, radiology scans, sometimes we can even find circulating bits of cancer cells in the bloodstream, but, most importantly, to treat a cancer we need a sample of tissue.

The saying tissue is the issue is all about the evolution of pathology and finding out how the group of cancer cells forms its own little being. What sex it is (what type of cancer)? Where does it live and how does it behave? 

So, we can kill this terrorist before it creates a body Armageddon.