New findings suggest PARP inhibitor drugs, used to treat cancer patients who have an altered BRCA1 or BRCA2 gene, may also be effective for patients which have changes in the SF3B1 gene.
If further research supports these findings, there is the potential that existing PARP inhibitor drugs such as olaparib, talazoparib and niraparib, might be able to help thousands more patients in the future.
The team at The Institute of Cancer Research, London, investigated changes in the SF3B1 gene, which are linked to several cancer types, including some oestrogen receptor positive (ER-positive) breast cancers and some types of leukaemia and melanoma.
The researchers discovered that PARP inhibitor drugs reduced the ability of cancer cells with an altered SF3B1 gene to survive.
Cancer cells unable to copy their DNA
One of the ways PARP inhibitors work in cancer cells with changes in their BRCA genes is by preventing them from repairing their DNA, leading to a build-up of damage and causing the cells to die.
Cells with an altered SF3B1 gene also lack a protein called CINP, which is important for regulating the cells’ response to PARP inhibitors. Without CINP, cancer cells aren’t able to properly copy their DNA when treated with the drug.
The team found that the PARP inhibitor drug talazoparib stopped the growth of tumours and prevented the cancer spreading in mice with uveal melanoma and leukaemia tumours with the altered SF3B1 gene.
Clinical trials in more cancer patients
Estimates show that SF3B1 gene changes affect around 3% of women with primary breast cancers and around 7% of those with incurable secondary (metastatic) breast cancer. They can occur in up to 20% of patients with some types of melanoma that affect the eye and also leukaemia.
Dr Phil Bland, the first author and postdoctoral training fellow in the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research, London, said: “As PARP inhibitors are already approved for use for some patients with changes in their BRCA1 or BRCA2 genes, we hope to soon begin a clinical trial to establish their benefit in a wider group of cancer patients. If these are successful, we hope to see PARP inhibitors made available to more patients relatively quickly.”
Edited by: Diana Spencer, Senior Digital Content Editor, Drug Discovery World
Image shows: A false-coloured scanning electron micrograph of a breast cancer cell. Credit: Anne Weston, Francis Crick Institute via the Wellcome Collection.