Science Surgery: ‘What’s being done to use treatments in different types of cancer?’

Our Science Surgery series answers your cancer science questions.

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Anna asked: ‘What’s being done to use treatments for one cancer in other types of cancer? For example, could a treatment for breast cancer be used in bowel cancer?’

Testing existing cancer treatments in other types of cancer is happening more and more. It’s a popular approach because it can be quicker than developing new treatments. With information about a drug’s safety, side effects and dosing already collected in people with one cancer, early safety trials can often be skipped in another.

But there’s no guarantee that what works for one cancer will work for others. Even though all cancers share the basic feature of cells growing and dividing uncontrollably, they also differ in many ways too.

That’s why the research that turns a treatment for one cancer into a treatment for another is all about finding the things cancers have in common.

Scientists are coming at this from different angles, from exploiting similarities in how the body ‘sees’ cancer to targeting faults that are shared by cancer cells growing in different parts of the body.

A helping hand for the immune system

Treatments that help the immune system kill cancer cells have received lots of attention in recent years. And part of the excitement around these new immunotherapy drugs lies in their potential to target multiple types of cancer.

“Targeting the immune system lends itself to being useful in different cancers, because the basic process of triggering the immune system is the same no matter where you are in the body,” says Dr Edd James, a Cancer Research UK-funded expert on the immune system from the University of Southampton. “We know a lot about how the immune system works, and why it might not work.”

One of the challenges the immune system faces is not being able to see cancer as something that needs to be destroyed. Some cancer cells can communicate with immune cells through molecules on their surface, telling them not to attack. This allows the cancer cells to survive and multiply.

Scientists have developed drugs, called checkpoint inhibitors, to disrupt these messages.

If a tumour, or the immune cells that burrow into it, carry these molecules, checkpoint inhibitors could help the immune system to kill cancer more effectively. Scientists have found one of these molecules, called PD-1, in samples from a small proportion of lots of different cancers.

Where PD-1 can be found in a sample, drugs such as pembrolizumab (Keytruda) and nivolumab (Opdivo) could help. These drugs are already used to treat some people with lung cancer, melanoma, Hodgkin lymphoma and kidney cancer in the UK. And they’re being tested in lots of others, including bowel, breast and head and neck cancer.

In the US in 2017, pembrolizumab was approved to treat any tumour with a certain type of genetic damage in its cells, regardless of where the cancer is growing in the body. This was the first time a drug has been approved based on a particular type of genetic ‘fingerprint’ irrespective of the type of cancer.

While checkpoint inhibitors are being tested in lots of cancers, not everyone’s cancer will respond to the treatment. Researchers are now trying to understand why, in the hope of boosting the number of people who could benefit from immunotherapy.

Zooming in on a cancer’s weak spots

Scientists are also looking at how treatments might be able to target faults that cancer cells share. This can be a molecule that’s gone wrong inside the cancer cells, or faults in the signals they use to multiply.

“Scientists are working to identify the fundamental building blocks that turn a normal cell into a cancer cell,” says James. “And there’s a good chance that some of these will occur in multiple cancers.”

One example of this is a molecule called BRAF, which is found inside cells and plays a key role in controlling how they divide. It goes wrong in around 5 in 10 melanomas and 1 in 10 bowel cancers. BRAF defects have also been found in some lung, ovarian and thyroid cancers.

Drugs that switch off one faulty version of BRAF (such as vemurafenib (Zelboraf)) are now used to treat some patients with melanoma that has spread and can’t be removed by surgery.

These drugs have also been tested in bowel cancer, but the results tell a different story.

Not as simple as it sounds

According to Professor Charles Swanton, Cancer Research UK’s chief clinician, there’s no guarantee a treatment will work in the same way in different cancers, even if the cancer cells carry the same defect.

“If we take the example of BRAF inhibitors, BRAF inhibitors work in melanoma but not nearly as well in bowel cancer, even though both tumours have the same mutation,” he says. “And that’s because different organs, and therefore the tumours that grow in them, are wired differently.

“Bowel cells rely on different signals to skin cells, which makes bowel cancer less sensitive to BRAF inhibitors.”

That’s why lab research and clinical trials are so important. Scientists can use cancer cells, lab-grown replicas of tumours called organoids, as well as animal models to do early tests of the effects of a drug. This helps test the potential of a treatment and decide if it should be taken forward and tested in clinical trials.

Old drug, new tricks

Researchers are also getting creative with how they test existing drugs in different cancers. Professor Anthony Chalmers, a Cancer Research UK-funded expert from the University of Glasgow, is testing a different type of targeted treatment, called PARP inhibitors, in glioblastoma – the most aggressive type of brain tumour.

PARP inhibitors stop a cell from repairing damage to its DNA. And the drugs are used to treat some breast and ovarian cancers that already have faults in the way they repair DNA.

But they don’t work by themselves in cancers that don’t have this defect.

“We’ve been looking at PARP inhibitors in a different way – using them to make radiotherapy and chemotherapy more effective,” says Chalmers.

“Both chemotherapy and radiotherapy work by damaging DNA, but sometimes they’re not enough to kill cancer cells.

“Using PARP inhibitors, we think we can make glioblastoma cells more sensitive to both radiotherapy and chemotherapy, and hopefully improve tumour control.”

Read more about Professor Chalmers’ work: scientists are combining drugs and radiotherapy, hunting for better results.

A new way of working

The more detailed our understanding of cancer gets, the more common features scientists will identify. And this could shift how clinical trials are run.

Scientists are starting to run trials based around specific faults (mutations) in the DNA of cancer cells, regardless of where the tumour is growing in the body. This approach can be useful when the fault in question is rare.

US scientists recently found that a new targeted drug, called larotrectinib, led to responses in a small number of advanced cancers that carry one of these rare gene faults. To test the drug, researchers carried out a series of small trials involving 55 patients with 17 different types of cancer.

Developing and testing a drug in this way is different to many trials, which usually focus on a specific type of cancer.

The lowdown

Testing treatments developed for one cancer in other types of cancer is a growing area of research. But like all research it’s a complicated picture.

Before an existing cancer treatment can be used to treat a new type of cancers researchers need to:

• Look and see if the fault the drug is targeting is present in other cancers
• Do early lab tests to investigate if the drug could work in other cancers
• Run clinical trials to test if the new drug works

“Essentially it just comes down to knowledge,” says James. “What we’re attempting to do with research is unpick all the mechanisms in a cancer. And with that knowledge we can identify targets that might lead us to treatments.”

Katie

We’d like to thank Anna for asking this question. If you’d like to ask us something, post a comment below or email [email protected] with your question and first name.