GLOBAL NEWS: OVARIAN CANCER RESEARCH

Researchers at the Walter and Eliza Hall Institute in Melbourne have developed a method to predict which ovarian cancer patients may develop resistance to PARP inhibitor (PARPi) therapy, by analysing tumour DNA in the blood.

PARPi is a commonly used targeted therapy for treating ovarian cancer with certain genetic mutations in DNA-repair genes, such as BRCA. PARPi’s work by stopping the cancer cells from repairing themselves, ultimately leading to cancer cell death. Common PARPi’s on the market include Olaparib and Niraparib. 

Genetic defects such as BRCA make the cancer cells more vulnerable to the effects of PARPi initially; however, many patients will eventually develop PARPi resistance.  

This research showed that specific changes could be detected in blood tumour DNA – notably, mutations that lead to ‘exon skipping’ in the BRCA1 gene. Exon skipping allows cells til 'skip' over faulty or misaligned sections (exons) of genetic code, leading to a function protein despite genetic mutation. In this case, versions of the BRCA1 protein were still functional, allowing cancer cells to repair their DNA enough to survive PARPi treatment. By identifying the mutations that cause exon skipping in circulating tumour DNA through a simple blood test, doctors may be able to predict treatment outcomes and adjust therapies accordingly. 

Understanding how ovarian cancer becomes resistant to PARPi is crucial for improving and expediting treatment strategies. While most resistance mechanisms involve fixing the damaged gene, the team identified another mechanism where cancer cells 'bypass' the problem by skipping the defective parts of the gene. 

This innovation not only offers a potential biomarker for PARPi resistance but also opens the door to more personalised treatment strategies, ensuring patients receive the most effective therapies at the right time. The findings can be immediately applied to tests already available in research settings, such as DNA sequencing of a patient’s tumour or detecting cancer DNA in the blood. 

Researchers from the Barts Cancer Institute in London have found that targeting specific immune cells in ovarian cancer can enhance the effectiveness of chemotherapy and improve outcomes. This approach could offer new hope for patients whose cancer doesn’t respond well to standard treatments, by boosting the body’s anti-cancer immune response. 

While chemotherapy is often used to treat High Grade Serous Ovarian Cancer – the most common subtype of ovarian cancer – it doesn’t always work as effectively as needed. Immune cells in the tumour environment play a key role in how ovarian cancer responds to treatment, but we don’t fully understand how these cells are affected by chemotherapy or how these can be targeted to improve outcomes. 

Researchers at the Barts Cancer Institute studied immune cells from ovarian cancer tissue samples to see how they change in response to chemotherapy. Using advanced single-cell sequencing technology, they analysed over 64,000 cells from patient tumours and discovered two key changes in types of immune cells – macrophages and T cells. 

They noticed increased levels of the STAB1 macrophage and higher levels of the FOXP3 regulatory T cells. Laboratory experiments showed that blocking STAB1 turns macrophages into cancer-fighting cells, while targeting FOXP3 reprograms T regulatory cells to stop their immune-suppressive activities. The team then tested whether treatments that target STAB1 and FOXP3, combined with chemotherapy, could improve outcomes. 

The combination of chemotherapy with treatments targeting STAB1 and FOXP3 significantly improved survival in mice with ovarian cancer. Tumours in treated mice showed more cancer-fighting immune cells, creating a stronger anti-cancer response. Their immune systems were also strong enough to stop the cancer from returning.  

This research provides a promising new approach to treating ovarian cancer by combining chemotherapy with therapies that boost the immune system. By targeting specific molecules on immune cells, this strategy could help patients whose cancer doesn’t respond well to standard treatments.