New gene technology is able to predict the effect of treatment on the individual breast cancer patient

When doctors find a genetic mutation in a woman suffering from breast cancer, they will try to determine whether that mutation is the cause of her cancer.

Mutations are often found in the so-called BRCA genes. A mutation in a BRCA gene can greatly increase the risk of breast cancer and ovarian cancer. But there are thousands of different mutations in the BRCA genes alone, and the majority of these mutations do not increase the risk of cancer.

“When a young woman has been diagnosed with breast cancer, the doctors will analyse her genome to see if there are any mutations. But in more than 50 per cent of the cases, they are unable to tell whether such mutations have anything to do with the disease,” explains Associate Professor Morten Frödin from the Biotech Research & Innovation Centre, who is one of the researchers behind the new gene technology, CRISPR-Select. The new technology has just been published in Nature Genetics, a major scientific journal at a global scale.

Frödin and his colleagues from the University of Copenhagen have solved the puzzle. Their new technology can help determine whether a particular mutation is indeed the cause of the disease. It can also reveal whether a highly effective form of cancer treatment will be able to kill the cancer cells.

“This is a significant improvement, as the gene technology can quickly tell us whether the mutation in the given cancer is sensitive to precision medicine. It is a form of treatment that we have been reluctant to use, both because it is expensive, and because we do not know whether it will be able to kill the cancer cells in question,” explains Associate Professor Claus Storgaard Sørensen from the Biotech Research & Innovation Centre, who is one of the other researchers behind the new technology.

Precision medicine is also called personalised medicine, and it refers to a type of treatment that is tailored to specific genetic mutations that cause cancer. In connection with breast cancer, personalised medicine is often targeted at a specific protein used by the cells to repair DNA damage and thus kill the cancer cells. But it only works if the mutation is indeed the cause of the disease.

May improve breast cancer treatment

The new technology solves a long-standing problem in cancer treatment. Because even though personalised medicine is an effective form of treatment, doctors have been unable to predict quickly and accurately whether it will work.

“For around 15 per cent of BRCA mutations found in breast cancer patients, doctors are able to conclude that the mutation is indeed pathogenic. For another 15 per cent, they are able to conclude that the mutation is not the cause of the disease. And for the remaining 70 per cent or so, doctors are unable to say anything about the impact of the mutation in question. In other words, they do not know whether it is harmless or harmful and the cause of the cancer,” says Morten Frödin.

This inability to determine whether such a large group of mutations are either harmless or pathogenic complicates cancer treatment. Therefore, doctors at Rigshospitalet in Copenhagen are already busy testing the new technology.

“We want to help make sure that as many patients as possible receive targeted, effective treatment. But treatment should only be administered when there is reason to believe that it will work. And we can only predict the effect of treatment when we know that the mutation is pathogenic,” explains Consultant Doctor Maria Rossing from the Center for Genomic Medicine at Rigshospitalet and adds:

“We are unable to determine the impact of most of the mutations we find. That is not satisfactory, and we find these mutations every single day. So we hope we will soon be able to use the new method in clinical practice, and that it will help support a large-scale development enabling us to determine whether a mutation is indeed pathogenic and whether treatment will work.”

This is a significant improvement, as the gene technology can quickly tell us whether the mutation in the given cancer is sensitive to precision medicine

The researchers hope the technology will enable doctors to use the available effective personalised medicine on more patients than is the case today.

Greater perspective

Cancer is the result of mutations, which are minor errors that occur when cells divide and turn into new cells. This process continues throughout life. Therefore, the new technology will also prove useful in treatment of other cancers and not just in connection with identified mutations in the BRCA genes in breast cancer.

“Treatment of many other forms of cancer face the same challenges. Using the new technology, we will be able to determine the impact of a mutation in these forms of cancer too and do a test to see if a particular treatment will be able to target the mutation in question. This principle can be used in connection with lots of different cancers and help give us a precise answer,” says Claus Storgaard Sørensen.

Morten Frödin adds that the perspective for the new gene technology is even bigger:

“Mutations in around one fourth of all our genes can lead to disease – altogether around 5,000 different diseases. And in all cases, doctors face the same problem. They rarely know which mutation has caused the disease, but in most cases the new method will be able to tell them,” says Morten Frödin and adds:

“That is the greater perspective, and that is what makes this method so applicable.”

The study “Multiparametric and accurate functional analysis of genetic sequence variants using CRISPR-Select” has been published in Nature Genetics.

Contact

Associate Professor Morten Frödin
morten.frodin@bric.ku.dk
+45 71 47 69 71

Associate Professor Claus Storgaard Sørensen
claus.storgaard@bric.ku.dk
+45 35 32 56 78

Journalist and Press Officer Sascha Kael Rasmussen
Sascha.kael.rasmussen@sund.ku.dk
+45 93 56 51 68