Researchers from Melbourne’s Peter MacCallum Cancer Centre have revealed a potential new treatment option for some women with the most lethal form of ovarian cancer, using a class of therapies already clinically approved to treat blood cancer.
Senior author of the study, Professor David Bowtell, says the findings, published this morning in Proceedings of the National Academy of Sciences, reveal that in a subset of women with high-grade serous carcinomas, the growth of their cancer is dependent on the activity of the BRCA1 gene.
‘In women with high-grade serous ovarian cancer, ten to 20 per cent of cases are driven by amplification of the Cyclin E1 gene, and about 20 per cent of patients have mutations that inactivate BRCA1 or BRCA2 genes — recently it has been shown that BRCA1 mutations and Cyclin E1 gene amplification rarely occur in the same patient.
‘By screening tens of thousands of genes, we found that cancers with Cyclin E1 amplification were particularly dependent on an in-tact BRCA1 gene — if the tumour has amplified Cyclin E1 and also mutation of BRCA1, then the cancer cells can not survive.’
Lead author, Dr Dariush Etemadmoghadam (pictured) says researchers sought to exploit the dependency of Cyclin E1 amplified cancers on BRCA1 to develop a new therapeutic approach for these tumours.
‘Recent research has shown a class of drugs known as proteasome inhibitors — approved to treat multiple myeloma in humans — are very effective at inhibiting the pathway involving BRCA1 and our laboratory experiments confirmed these drugs are effective for treating Cyclin E1 amplified tumours.
Professor Bowtell says there is great need for new therapeutic approaches for women whose ovarian cancer has Cyclin E1 amplification.
‘Women in this subset generally have poor response to standard treatment and reduced survival rates, so we are hopeful this new approach can be tested in a clinical trial in the near future.
‘We now know ovarian cancer is a very diverse disease, analogous to a Russian babushka doll — it looks like one doll until you take it apart and find layer after layer — but we’re confident when we have finally separated this cancer into all its molecular groups, we will have a much better chance of improving survival for all women.’