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This entry is part 5 of 6 in the series Science Snaps

They may look like pictures from a strange forest on another planet, but these illustrations depict a key process in all our cells that dictates when a cell will grow, divide or move.

It’s tightly regulated, but if faults arise then cells can grow and divide out of control – a hallmark of cancer.

In this guest post, Emily Burns and Jeroen Claus – PhD students from our London Research Institute – explore this molecular wilderness revealing the science behind the illustrations and how it’s being translated into the targeted cancer treatments of the future.

‘Personalised’ or ‘precision’ medicine is a hot topic in cancer treatment.

It holds the potential to specifically target the cancer-causing molecules driving each patient’s tumour.

Rather than using a single therapy across the board, each patient could receive a treatment tailored to their cancer – even allowing us to target more than one molecule at the same time.

In our research we study the intricate shapes of these potentially cancer-causing proteins, looking for new ways to spot the weaknesses that could be exploited by the targeted treatments of the future.

How it all begins

Each one of our cells is covered with molecules known as protein receptors. These receptors receive signals from outside the cell and relay the messages inside.

Their messages are diverse, including instructions such as “Grow”, “Multiply”, or “Move that way”.

The recipe for these cell surface receptors – along with every other protein in our body – lies in our genes, encoded within our DNA. But mistakes in the DNA code, known as genetic mutations, can lead to errors in these receptors: there can be far too many of them, or they can become constantly active.

Imagine a person holding a megaphone, shouting instructions. Now imagine there are 1000 times more of them: that message is going to be a lot louder.

This is shown in the illustrations below, and is exactly what can happen on some cancer cells.

designerdrugsmerge

On the left is what the surface of a healthy cell might look like – the number of blue receptor molecules is tightly controlled. But on the right is what happens on some cancer cells – the receptors are produced in huge excess, resulting in much louder messages being sent inside the cells.

And louder messages result in more cells multiplying, which lead to uncontrolled growth. This is how a tumour develops.

It’s the same for faulty receptors becoming constantly active: the message is no longer switched off, so it continuously tells cells to grow.

It’s in the detail

Scientists now have an increasingly better idea of the types of receptor that can become mutated. One receptor that we’re particularly interested in is called HER2 – the blue ‘trees’ in our images.

In about one in five breast cancer patients there are far too many HER2 receptors, constantly telling the cells to multiply. In order to target HER2 specifically, we need to know what it looks like, so that a drug can be designed to mute the signals it is sending into the cell.

Scientists are able to look at the unique details of HER2 on an incredibly intricate molecular level, using a technique called X-ray crystallography. In doing so, they can create a snapshot of the active part of the protein and tailor-make a drug that will sit within it, preventing the receptor from working.

One such drug is called lapatinib. It acts as a molecular plug, sitting deep within the active region of the receptor. Lapatinib is just one of the drugs available in the growing arsenal of precision treatments, which target specific cancer-causing proteins.

Drugs that work along similar lines are also used to treat people with particular types of leukaemia, lung cancer, bowel cancer and skin cancer.

Testing the treatments of the future

A big challenge is finding out who will and who won’t benefit from these types of treatment.

It is now possible to extract DNA from a patient’s tumour and find out which receptors have been mutated. This can give doctors very specific information about a particular patient’s disease, and can reveal if there is a targeted drug available that may be suited to their tumour.

Yesterday Cancer Research UK launched the latest stage of its Stratified Medicine Programme with an ambitious clinical trial to link this kind of molecular diagnosis with potential new treatments for late stage lung cancer patients.

But in many cases this isn’t straightforward.

We now know that different regions of the same tumour can carry different genetic faults, making the process of identifying which drugs to use very difficult.

And tumours can adapt, becoming resistant to these more personalised treatments. Scientists are working hard to understand how this happens by spotting the tricks these proteins play to avoid our designer drugs.

By refining the design we hope that more patients can be treated with drugs tailored to their disease in the future, increasing survival and bringing cures closer.

Emily Burns and Jeroen Claus

Image credit: Jeroen Claus – images were originally created in collaboration with the Francis Crick Institute for ‘Bio-Revolution’ at the Science Museum Lates in February 2014.

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