Harder, better, faster, kinder – a new era for cancer drug testing

Discovering and developing new cancer drugs takes a lot of time, money and effort.

From a collection of chemicals that might kill cancer cells in the lab right through to a drug that is safe and effective for patients, the process can take more than 10 years. And cost millions of pounds.

But a study from a team of our scientists, published today in the journal Cell, points to a new way to test hundreds of cancer drugs quicker than ever before.

The work – led by Professor Carlos Caldas at our Cambridge Institute – is already being used to test new breast cancer treatments.

And it could dramatically reduce the time it takes to test new drugs for other types of cancer too.

The problem

All new cancer drugs start life in the lab, where they are first tested on cancer cells. These different cell lines may have originally come from samples of patients’ tumours, but they have been modified so they can grow indefinitely in a Petri dish.

Testing cancer drugs in cell lines gives us an idea about whether or not they have potential. But it’s not ideal – Professor Carlos Caldas

For decades, these cells have been an invaluable resource in the fight against cancer, helping scientists understand more about the disease and how to treat it. Scientists use cell lines to study how cancers grow and develop, and to test whether new drugs work or not.

An advantage of cell lines is that they can grow indefinitely, meaning scientists have an endless supply of them available for their experiments. This also means they can use cell lines to test lots of different drugs at the same time – something called high-throughput drug screening.

But as science has progressed, so has our understanding of cell lines. Researchers now know that while cell lines are a vital tool in cancer research, they have their limitations.

“At the moment, cell lines are one of the best tools we have for studying cancer cells in the lab,” says Caldas. “But they are grown on plastic dishes in the lab, in an artificial setting. This is completely different from the extremely complicated way cells grow inside a patient’s body.”

This becomes a problem when scientists are testing new potential cancer drugs. Because the lab-grown equivalents don’t completely mimic how cancer cells behave in patients’ bodies, testing drugs in cell lines doesn’t give researchers all the information they need.

“Testing cancer drugs in cell lines gives us an idea about whether or not they have potential,” Caldas explains. “But it’s not ideal – it doesn’t compare to testing drugs directly on cells taken from people with cancer.”

So why don’t scientists take cells from patients’ tumours and directly test drugs on them instead?

The answer is they can and they do – but this approach also has its limitations.

Put simply, cells taken from patients are rare and harder to come by. This means testing lots of different drugs in various combinations isn’t possible using cells from patients.

On top of this, these cells are notoriously difficult to work with in the lab – they don’t grow very well or very often, which means you can only do each experiment once. And experiments involving them tend to be quite slow and laborious.

This means scientists are trying to develop new cancer drugs in settings that either don’t reflect how cancer behaves in patients or in settings that aren’t practical for testing lots of drugs.

Faced with this problem, Caldas and his team have developed a new, better way to test hundreds of cancer drugs. Crucially, their approach more closely mimics how cancer cells behave in patients, and can be done more quickly than other methods.

A new solution

The team’s approach centres on first growing cells from patients in mice. This produces many more copies of the cells than would be possible in a lab dish, allowing the team to take these cancer cells and use them to test hundreds of different drugs.

And in the latest study, the team used cancer cells from women with breast cancer who took part in large Cancer Research UK-funded study that redefined breast cancer as 10 different diseases – the METABRIC study.

Excitingly, they found that cancer cells grown in this way more accurately reflected the genetic faults seen in patients’ tumours, and how these cells grow and behave in the human body, compared to cell lines.

The team also found that this method could be used to produce enough cells for large-scale drug testing, unlike typical samples of cancer cells taken from patients’ tumours.

“The cancer cells we took out of the mice closely resembled the original cells present in breast cancer patients’ tumours,” says Caldas. “This gave us confidence that our new method would allow us to test hundreds of drugs and drug combinations in cells that were very similar to those found in the original tumour.”

This, says Caldas, will help speed up the team’s efforts in identifying new cancer drugs.

“They could reach the patients who need them faster,” he adds.

“We believe that in time, this new method of developing and studying cancer cells will replace traditional methods of growing cells in plastic dishes.”

Where to next?

This work used breast cancer cells from patients. And from it, the team has developed cells that match each of the 10 different types of breast cancer originally identified in the METABRIC study. They now plan on using these cells to identify the best drugs, or combinations of drugs, to tackle each of these different subtypes.

“When we discovered that there are 10 different breast cancer subtypes, our aim became to find drugs and drug combinations specifically tailored to each of the subtypes,” explains Caldas.

“Now that we have developed our new method, we can do this faster than ever before. And we can be confident that we’re testing these drugs in a more accurate setting.”

Once the team has identified which drugs work best for which subtype in the lab, they then plan on taking the drugs forward into clinical trials in patients to find out if they can help save lives.

And it’s not just women with breast cancer who could benefit from this new technique – the potential could be much bigger.

Caldas and his team are making all the details about their new method – and any data they get from it – available to other researchers around the world.

“We hope that by doing this we can help others find better treatments for many different types of cancer sooner.”

Áine