Why is cancer so hard to treat?

As a cancer scientist, a common question I get is “When are we going to cure cancer?”. It sounds like a simple question, but the truth is pretty complicated.

The first thing to point out is that finding a cure for cancer is extremely unlikely. Cancer is an umbrella term for over 200 different diseases (1000s of different diseases if you include sub-types). Although these diseases have many outward similarities (all grow uncontrollably and have the potential to invade and spread), the biological mechanism is different for most cancer types. The simple answer is that we may find cures for various cancers, but each will need their own research and treatment strategies.

To understand cancer you have to understand that it is a disease of evolution. Over the past 4 billion years we have evolved from a single celled organism to the dominant mammals on the planet. This process is driven by random alterations and mutations of our DNA. Each of these mutations has the potential to change our genetics. If that change gives an individual an advantage over the rest, then that individual is more likely to survive and to pass the advantage on to his or her offspring. This selective pressure to retain advantageous traits is known as “Natural Selection”.

These random changes and mutations can happen every single time a cell divides. Our cells are actually astonishingly efficient at avoiding and correcting mistakes, preventing most events that could result in a tumour. However, trillions of our cells divide every single day, and not all mutations can be caught.

Just like in our evolution, if a mutation gives one of your cells an advantage over the other cells, then this cell will survive over the cells around it. For example, if a mutation causes a cell to multiply out of control, it will outgrow those around it and form a tumour. Moreover, tumours can often result from unique combinations of mutations, which will drive their growth in a different ways.

If you take a step back and think about that, you can begin to see why a cancer can be so hard to treat. It is a corruption of our own cells, genetically almost identical to healthy ones, similar enough to make it hard to target, different enough to drive the disease. Most drugs we try to use will have difficulty differentiating between cancer and healthy cells, and as a result will cause terrible side effects.

To make things even more complicated, as the tumour itself grows it accumulates more and more mutations. Some of these mutations will cause further advantage over other cells within the tumours, and form their own little part of the growth, meaning that the cancer can be made up of many cells that are genetically different.

Resistance from Scientific American
From http://blogs.scientificamerican.com/overthinking-it/what-starcraft-can-teach-gamers-about-fighting-cancer/

This brings us back to the idea of natural selection: when we find a drug that works for a tumour, we are applying a selective, evolutionary, pressure. If any of the different cells in the cancer allow it to resist the therapy, then that cell will quickly take over, giving rise to a chemo resistant cancer (pictured).

Tackling this problem requires an understanding of the various mutations that are causing the cancer to grow. This understanding allows us to design drugs towards these specific mutations, a process we have already started. If we can then recognise what mutations are present in a specific tumour (using techniques like liquid biopsies, which we have written about before), we can use this new generation of drugs to target all of the different mutations present. This may, for the first time, allow us to design a treatment specifically aimed at stopping resistance arising.

Vast resources are now being invested in developing these targeted therapies. There already have been some significant successes. For example, breast cancer, lung cancer and melanoma patients can now get different drugs depending on the mutations present in their tumours. It is unlikely that we find one drug that will cure cancer, but research in this direction will help us to refine treatments and ultimately improve patient survival.

 

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