Unravelling ovarian cancer reveals potential new treatment

Researchers have taken another step towards understanding ovarian cancer, and in treating one of the most lethal forms of this elusive disease.

The findings by researchers from Melbourne’s Peter MacCallum Cancer Centre build on the understanding that some ovarian cancers are driven by the deactivation of the BRCA 1 gene, especially those with high-grade carcinomas.

‘We now know ovarian cancer is a very diverse disease, analogous to a Russian babushka doll,” said Professor Bowtell, senior author of the study, which was published this week in Proceedings of the National Academy of Sciences.

“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.”

In explaining their study, Professor David Bowtell said “In women with high-grade serous ovarian cancer, 10-20% of cases are driven by amplification of the Cyclin E1 gene.”

On the other hand, about 20% of patients have mutations that deactivate BRCA1 or BRCA2 genes.

“Recently it has been shown that BRCA1 mutations and Cyclin E1 gene amplification rarely occur in the same patient,” said Prof Bowtell.

Professor Bowtell and his team screened tens of thousands of genes and revealed that tumours with Cyclin E1 amplification were particularly dependent on an in-tact BRCA1 gene. They found that inhibiting BRCA1 was selectively toxic to the cells with excess cyclinE1 and so they sought to target this dependency.

They looked at a class of drugs known to treat multiple myeloma, and to target or inhibit active BRCA1 pathways. They found that the existing therapy effectively treated Cyclin E1 amplified tumours.

Professor Bowtell is hopeful that this new approach, which will bring hope to women with very poor responses to standard treatment, will move towards clinical trials in the near future.

The ACRF is proud to have funded, with $7.0 million in grants, the work of world-class research teams at the Peter Mac.