Actress Angelina Jolie had a preventative mastectomy in 2013 after testing positive for the mutated BRCA1 gene
There is hope for people with the ‘Jolie gene’ for cancer, from drugs which kill tumour cells while leaving healthy ones unharmed.
Around one in 200 people in the UK carry a mutation in the BRCA1 or BRCA2 genes, so have a higher risk of breast, ovarian, prostate and pancreatic cancer.
Actress Angelina Jolie had a preventative mastectomy in 2013 after testing positive for the mutated BRCA1 gene.
Now scientists have discovered a class of drugs which can destroy this type of cancer, and are set to be tested in clinical trials on patients at the end of this year.
The drugs are so badly needed because people with cancer caused by a BRCA mutation currently have only two main options for treatment.
These are chemotherapy and drugs called PARP inhibitors, which are only currently routinely available for those with ovarian cancer and do not work for everybody.
Where PARP inhibitors fail in people whose cancer had spread, the new drugs could provide a lifeline treatment.
Called POLQ inhibitors, they prevent cancer cells repairing themselves, while having no effect on healthy cells.
They have been found to destroy tumour cells taken from patients with breast, ovarian, prostate and pancreatic cancer, and the next step is proving they work within the body when taken as a pill.
Chris Lord, professor of cancer genomics at the Institute of Cancer Research in London, who co-led a study on the drugs, said: ‘A significant number of patients are given PARP inhibitors like the drug Olaparib for ovarian cancer and after a while they stop working.
‘The drugs we have identified could provide a much-needed new way to treat people with hereditary cancer, including those where PARP inhibitors have failed.’
Cancer linked to the BRCA genes runs within families, with Angelina Jolie’s mother having died from ovarian cancer at the age of 56.
People with faulty versions of the BRCA genes are at greater risk of cancer because they cannot repair damaged DNA in their cells.
What is the BRCA gene and how does it affect people’s risk of cancer?
Having a mutated BRCA gene – as famously carried by Angelina Jolie – dramatically increases the chance a woman will develop breast cancer in her lifetime, from 12 per cent to 90 per cent.
Between one in 800 and one in 1,000 women carry a BRCA gene mutation, which increases the chances of breast and ovarian cancer.
Both BRCA1 and BRCA2 are genes that produce proteins to suppress tumours. When these are mutated, DNA damage can be caused and cells are more likely to become cancerous.
The mutations are usually inherited and increase the risk of ovarian cancer and breast cancer significantly.
When a child has a parent who carries a mutation in one of these genes they have a 50 percent chance of inheriting the mutations.
About 1.3 per cent of women in the general population will develop ovarian cancer, this increase to 44 percent of women who inherit a harmful BRCA1 mutation.
It means they can develop abnormal cells, which grow rapidly to become tumours.
But the benefit of the BRCA fault is that it prevents cancerous cells, as well as healthy ones, from repairing themselves.
Happily, POLQ inhibitors do the same thing, leaving cancer cells no way to fix themselves so that they die.
Healthy cells, which still contain a normal copy of the BRCA gene, can repair their damage normally, so survive.
This avoids a major pitfall of chemotherapy, where both cancer cells and healthy cells are killed, causing side effects such as sickness and hair loss.
A major reason for new treatments being needed is that it is all too common for women with ovarian cancer which has spread to find the current drugs, PARP inhibitors, no longer work after a while.
But POLQ inhibitors could provide another line of defence, with both sets of drugs killing cancer cells by stopping them repairing their DNA, but POLQ inhibitors doing it slightly differently.
Mini-tumours grown in the lab which had mutated so that PARP inhibitors no longer worked on them were killed easily by POLQ inhibitors, according to the study published in the journal Nature Communications.
That suggests both drugs could be used together in the future as a super-treatment.
Clinical trials, led by pharmaceutical company Artios are due to start in the last three months of the year.
Michelle Mitchell, chief executive at Cancer Research UK, said: ‘We are always trying to find newer and better ways to outstep cancer, especially when it stops responding to current treatments.
‘By revisiting weaknesses in the BRCA repair pathway, researchers have not only found a way to make PARP inhibitors more effective, but they may have also identified an entirely new class of targeted drugs for BRCA cancers, which could include pancreatic cancer which has limited treated options.
‘We look forward to seeing if these promising results in the lab transfer into benefits for patients when tested in trials.’