New breast cancer drug could be ready within five years


The treatment, developed by Cancer Research UK, targets tumours caused by mutations in the BRCA genes – which prompted Angelina Jolie to have a preventative double mastectomy.

An effective new drug could be available within five years to treat the kind of breast cancer that prompted Angelina Jolie to have a preventative double mastectomy in 2013.

Women with faulty BRCA genes typically have a 45 to 90 per cent chance of developing breast cancer and some, including Jolie, have a preventative double mastectomy to reduce that risk when they find out they have the mutation.

Experiments on rats and on human cells in the lab found that the drug completely halted the growth of tumours caused by mutations in the BRCA1 or BRCA2 gene, which are responsible for around 2,750 new cases of breast cancer a year in the UK. Most cases occur in women but men can sometimes be affected.

The treatment has been created by scientists at Cancer Research UK and Artios, a spin-out it set up in Cambridge to develop the drug which has received £90 million of funding.

Artios will begin a major clinical trial later this year. The hope is that the drug can be used to treat a limited number of patients within two years, and become more widely available on the health service within five years.

However, researchers stressed that this was a “best case” scenario and cautioned that the process could take longer or be found not to work in living humans.

Nonetheless, they are excited by the potential for this new class of drug, known as POLQ inhibitors.

“I’ve been in drug research for 17 years and this is the most exciting project I’ve worked on,” said Mark Charles, an associate director at Cancer Research UK.

“It’s the first inhibitor in this particular class and the first one that will be going into the clinics. That’s always an exciting thing, when you get a ‘first-in-class’ molecule that no other company has.”

POLQ inhibitors curb the growth of tumours with BRCA gene defects by stopping them from repairing themselves.

When the BRCA tumour-suppressor gene is faulty, cancer cells utilise a protein called POLQ to repair damaged DNA, helping them to continue to grow and proliferate.

“There are so many different avenues to use for this inhibitor,” Dr Charles said. “It could be used in combination with radiotherapy and other drugs that treat patients in the clinic.

“Basically, POLQ is only expressed in cancer cells – it’s not highly expressed in other normal tissues – so the expectation is that the drugs will be tolerated very well and won’t have some of the other toxicities we sometimes observe with other cancer drugs.”

The researchers have shown that these drugs offer the potential to target tumours that have faulty copies of the BRCA genes while at the same time leaving healthy cells unharmed.

And, crucially, they can kill cancer cells that have become resistant to PARP inhibitors – an existing treatment for patients with BRCA mutations.

Dr Simon Vincent, director of research at Breast Cancer Now, which part-funded the study, said: “It’s hugely exciting that POLQ inhibitors could provide a targeted treatment option for people whose cancer is caused by altered BRCA genes. As a targeted treatment, we hope that POLQ inhibitors could be a kinder alternative, with fewer side-effects than current treatment options.”

“Drug resistance is a major hurdle that we must tackle to stop women dying from breast cancer, so it is also exciting that POLQ inhibitors offer a hope of overcoming resistance in some cases,” Dr Vincent added.

Michelle Mitchell, chief executive of Cancer Research UK, which also part-funded the research, said: “Although the drugs need to be tested in clinical trials, these findings are promising and we hope to one day see them translated into real-life benefits for breast cancer patients.”

Drug can be used for other kinds of cancer

The new class of drug that has been developed for BRCA-related breast cancer could potentially be used to treat some forms of ovarian, pancreatic and prostate cancer as well, researchers said.

As with breast cancer, BRCA gene mutations in these other conditions are only responsible for a small portion of cases, but put those who do have them at a much higher risk of the disease.

“This is extremely exciting – the possibility not only for treating breast cancer patients but other patients as well with BRCA deficiency,” said Mark Charles, of Cancer Research UK.

He says the drug could be applied to other kinds of BRCA cancer relatively quickly – and, potentially, some types that are not related to a deficiency of that gene – although it is far too early to know which ones.

Dr Charles said the new drug would initially be used by patients whose cancer had become resistant to existing treatments. But further down the line, assuming it is found to be effective, it could become a first-line treatment.

“Typically you don’t go in early on with a drug as a first-line treatment because you use drugs that are already known,” he said.

Scientists from the Institute of Cancer Research in London were also involved in the study, which is published in the journal Nature Communications.

Published on: 09.07.21

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