Hi I'm Selby
and I'm Rachel
We work here at The Institute of Cancer Research in London.
We work as part of a team of scientists
including biologists, chemists, computer scientists and medical doctors
to discover and develop new drugs to treat cancer.
In our bodies cells are dividing all the time – it’s a normal part of our body’s living process
but this process can go wrong.
Cancer occurs when a cell continues to divide without stopping
producing cells when the body doesn’t need them.
These cells can form lumps, which we call tumours.
Cancer can be treated in a number of ways:
using surgery,
radiation
and drugs.
A drug is a substance that causes changes inside the body.
They are crucial in our efforts to help people with cancer live longer.
At the ICR we discover new drugs for cancer,
but how do we do it?
First of all we compare cancer cells to normal, healthy cells
to identify any differences between them.
This helps us understand what’s powering the cancer
and helps us find targets for our new drugs.
A target is a biological molecule, like an enzyme or a receptor.
Our aim is to discover a drug that binds to the target and affects how it works,
disrupting the course of the disease.
For example, the ICR discovered a prostate cancer drug called abiraterone.
The target of abiraterone is an enzyme which helps prostate cancers grow.
We knew that this enzyme was making hormones
that were driving the cancer, so we designed a drug to stop it.
Targets are often proteins – biological molecules made up of amino acids.
Finding the right target is an essential stage in creating a new treatment.
It enables us to find a drug that affects cancer cells but leaves normal cells alone.
Once we have identified a target, we find out as much as possible about it.
We analyse its structure using X-ray crystallography –
a technique which gives us a picture of what the target looks like.
We use bacteria to make copies of the target, which we use to test our new drugs.
We then begin the search for a new drug – what we are looking for
is a molecule that will bind to the target and affect its action.
We test a large number of molecules to see if they bind to the target.
These act as a starting point for drug discovery
and together they make up what we call a library.
Usually there’s around 200,000 different molecules in the library we test.
By starting with so many we hope to identify one that binds to the target.
For a drug molecule and the target to bind to each other they need to fit together
like two pieces of a puzzle
or a lock and a key.
When the drug molecule and target fit together
we say that they are complementary.
Any molecule in the library that binds to the target will usually only bind weakly.
This is because the molecule and target won’t be a perfect fit.
So our next step is to modify our potential drug molecule
to improve the way that it fits its target.
Computer simulations help us make improvements to the drug molecule.
We produce 3D versions of the target and drug
where we can see every atom and bond within them.
These are developed using the X-ray crystal structures –
the pictures of what the molecules look like.
The computerised models can be used to look carefully
at how the drug molecule and target interact.
This helps us work out what changes we need to make to improve the fit.
We also need to consider the properties that make a good drug.
It needs to be soluble so that it dissolves in your bloodstream
it needs to be stable to your metabolism
so that it isn’t destroyed by the acid in your stomach or the enzymes in your liver
and finally, it needs to be permeable
so that it can travel through the cell membranes and get to the tumour.
Once we have designed and produced a drug molecule that binds to our target,
we need to test how well it works as a drug in cancer cells.
We test our new drug for two reasons –
to find out if it is effective at killing cancer cells
and then to test whether it is safe to give to people.
First of all we carry out experiments in the lab.
We test our new drug on proteins, which we have grown using bacteria
and then we test it on living cancer cells.
We do this many times
and each time we use the results from the tests to design a better drug.
Next, we test whether it is effective at shrinking tumours in animals –
usually mice and rats.
If the drug has worked in all of these experiments, we want to see if it works in people
but before we can do this, we need to make sure that the drug is as safe as possible
so we test the safety of the drug in two different animal species.
It’s the law in Britain that this testing is done before any new drug is given to people.
All of the animal experiments we carry out in drug discovery and development
are vitally important for progressing a new drug to patients,
and they are only used in research when it is completely necessary.
If the animal studies give us confidence that the drug is safe,
we can move forward to assess it in people as part of a clinical trial.
Clinical trials are designed to test:
The toxicity of a drug – so whether it is dangerous for people taking it
and what side effects it has.
The dose of a drug – so how much of it you should give to people.
And the efficacy of a drug – so how well it works against the disease,
which in our case is cancer.
There are three different stages, or phases, of clinical trials: phase 1, 2 and 3.
A new drug must successfully complete each phase of a clinical trial
before it can progress onto the next.
Phase 1 trials focus on the toxicity of the drug,
including any side effects and what happens to the drug inside of the body.
Only a small number of people take part in phase 1 trials.
They start by taking very small doses of the drug
and then build up to higher doses as we find out more about its effects.
Phase 2 trials include more people, who will always be the patients with the disease.
The aim is to find out the efficacy of the new drug, which is how well it works,
and confirm the dosage.
Phase 3 trials involve lots more patients
and focus on how the drug affects a more diverse population of people.
These trials are intended to build up strong statistical evidence
that a drug works in a particular group of patients.
In most clinical trials the first people to take a drug are healthy volunteers,
meaning that they don’t have the disease that the drug is designed to treat.
If the tests in healthy volunteers have shown that the drug is safe,
it can then be given to the patients who have the disease.
This is designed to test whether the drug works as intended.
Before a new drug can be used to treat patients,
we need to show that it's better than the current, best treatment
which we call the standard of care.
It can be hard to show this and so it’s really important to design clinical trials carefully.
The best way of showing this is by conducting a randomised controlled trial.
In these trials patients are split into groups who will receive different treatments.
One group, called the control group, will receive the standard of care
and the other group, called the treatment group, will receive the new drug we are testing.
Computer programmes are used to divide patients into the different groups
so that we can be sure it’s a completely random process.
In a double blind trial, which is a type of randomised controlled trial,
patients are split randomly into two groups.
One group takes the new drug, while the other group takes the placebo –
an inactive form of the drug being tested.
Neither the doctors nor the patients know who is in which group.
Researchers and doctors can then compare the two groups
to see which treatment is more effective.
Clinical trials for cancer drugs can be very different from clinical trials for other diseases.
Firstly, we don’t test cancer drugs in healthy volunteers.
This is because cancer drugs can have considerable side effects
and so it wouldn’t be fair for healthy volunteers to experience these.
Instead, the first people to take the new drug are patients with cancer.
Secondly, it’s not common to use placebos in cancer clinical trials.
This is because it’s better for patients to be treated with the standard of care,
rather than the placebo.
We analyse the results of clinical trials really carefully.
We use statistical tests to make sure that the results have not happened by chance.
It is important that the sample size, which is the number of people who take part in the trial,
is big enough to support what we are trying to show.
Then as a final step the drug needs to be licenced.
Regulators check all the trial data to make sure it’s safe for patients.
If the drug is approved then patients can start taking the new treatment.
We often collaborate with companies
when it comes to running large clinical trials of new drugs discovered at the ICR.
At the ICR we discover more new cancer drugs than any other academic centre in the world.
Since 2005, ten of our drugs have entered clinical trials
and many more current cancer medicines are rooted in discoveries made here.
There is a still lot of work to do to create tomorrow’s cancer treatments.
Our team continues to work hard every day to turn discoveries in the lab into
smarter, kinder and more effective treatments for patients.