Funded by us, a group of researchers have discovered that people with genetic changes in a gene called SF3B1 may benefit from PARP inhibitors.
The SF3B1 gene is linked to various cancer types, including oestrogen receptor positive (ER positive) breast cancer and certain forms of blood and skin cancer.
If more research supports this, PARP inhibitor drugs could help thousands more people with breast cancer and other cancers.
Finding the link
Changes in the SF3B1 gene affect around 3% of people with primary breast cancer, and around 7% of those with secondary breast cancer.
At our research centre, Dr Rachael Natrajan and her team tested 80 drugs to find which may be effective against cancers with an altered SF3B1 gene. The drugs they tested are all currently used in cancer treatment or late-stage development.
The researchers found that PARP inhibitors were effective at destroying cancer cells with changes to the SF3B1 gene.
Rachael added: "Our exciting findings show that PARP inhibitors can also exploit a weakness in cancer cells which have mutations in the SF3B1 gene. And suggest there may be a whole new group of patients, including those with ER positive breast cancer, who could benefit from this personalized medicine."
Understanding the mechanism
PARP inhibitors are a type of targeted therapy. They’re used to treat some people with breast, ovarian, or prostate cancers with an altered BRCA gene. PARP inhibitors work in cancer cells with changes in their BRCA genes by preventing them from repairing their DNA, causing the cells to die.
For the first time, the scientists at our centre found that even when cancer cells with the altered SF3B1 gene have normal BRCA genes, they were still weakened by PARP inhibitors.
They discovered this is because cells with an altered SF3B1 gene also lack a protein called CINP. Without this protein, cancer cells can’t properly copy their DNA when treated with the drug. This causes the cancer cells to stop growing and die.
Looking into the future
Now, the researchers hope to test the results of this study in clinical trials. In the future, this means that existing PARP inhibitor drugs could potentially help thousands more people, including those with ER positive breast cancer.
Dr Simon Vincent, our director of research, support and influencing added: “PARP inhibitor drugs have been shown to save the lives of women with certain types of early breast cancer, so it’s incredibly exciting that even more patients could potentially benefit from them in the future, including those with the most common type of breast cancer. Further research is now needed to understand more about how they could help people with different types of cancer and possibly transform the way the disease is treated.”
The study was published in Nature Genetics and was funded by Breast Cancer Now.
Breast Cancer Now thanks Art For Cure for their generous support of Dr Natrajan's research.