Post-doctoral researcher Jess Beach, who specialises in ovarian cancer, moved across the globe to work with Peter Mac’s Professor David Bowtell. She has just started her first clinical trial in ovarian cancer: Targeting the C1 Subtype of High Grade Serous Ovarian Cancer (BEACON).
Find out about Jess’ path to becoming a scientist and then uprooting her life in the United States to come to Melbourne to work at Peter Mac.
How did you become interested in science?
My interest in science is from my Dad. He's a marine biologist and when we were kids he was always showing us things like whale eyeballs in jars. Through my Dad’s work I got my first introduction into genetics and molecular genomics working in a summer internship where I genetically profiled salmon populations in Washington state and it really sparked my interest in this area.
I did track and field in high school and got an athletic scholarship to go to university in California. Then from there I applied to Cedars Sinai Medical Center for my PhD. Because it's a Jewish hospital we actually did a lot of genomics work on BRCA1and BRCA2 because the Jewish population are high frequency carriers of those genes, which are both genes that promote ovarian and breast cancer in females and breast cancer in males.
Why did you decide to come and work at Peter Mac?
I did my PhD at Cedars Sinai in ovarian cancer there, which is how I knew about Professor David Bowtell. What was really exciting was the Australian Ovarian Cancer Study, where they have collected close to 3000 cancer samples from women all over Australia who have high grade serous ovarian cancer. These samples are a really powerful tool because for a lot of the research that we do (in the US), we only have small numbers and can't say if something is a significant finding. But when we have a large number of samples, such as in the Australia Ovarian Cancer Study, you can make those discoveries and you have a large enough data set that they are significant, and they can change how medicine is practiced and how things are treated.
I really wanted to come to Peter Mac to continue my post-doctoral research so I cold called David and said I'm really interested in ovarian cancer research and the AOCS. I was also really attracted to working in a research institute that's within a hospital as I want to have that patient interaction and the ability to collect samples from patients as well. I just told David I wanted to come and he said ‘sure’ and that was that.
I actually just got permanent residency so the plan is to stay long term. People always say the US is where they want to go to do science but I feel that the science here is equal to surpassing the research that's going on there.
You’ve just started your first clinical trial at Peter Mac: Targeting the C1 Subtype of High Grade Serous Ovarian Cancer (BEACON). Tell us about it.
The majority of women diagnosed with high grade serous ovarian cancer present with advanced disease, and are typically managed with a combination of surgery and platinum-based chemotherapy. Despite initial good response rates to chemotherapy, high grade serous ovarian cancer recurs in up to 70% of patients who present with Stage III/IV disease.
The molecular characteristics of high grade serous ovarian cancer have recently been extensively described in multiple studies. One of the consistent features identified are four distinct molecular subtypes that are based on gene expression profiles. These four subtypes are associated with differential clinical outcomes that are largely consistent across multiple datasets. The subtypes may also be predictive for benefit from certain types of treatment.
The "C1" or mesenchymal subtype is characterised by an excessive fibrotic response of the stroma (connective tissue) surrounding tumours, a process that is collectively referred to as desmoplasia. Patients with the C1 subtype of high grade serous ovarian cancer have an increased incidence of primary treatment failure and poor overall survival (OS).
The purpose of this clinical trial is to test how safe and effective the combination treatment of drugs cobimetinib, bevacizumab and atezolizumab is as a treatment for patients with a C1 subtype of platinum resistant or refractory ovarian, fallopian tube or peritoneal cancer. We are aiming to recruit 30 patients to BEACON over the next two years, with full completion of the study estimated in 2023.
Cobimetinib, bevacizumab and atezolizumab have been used alone or in combination in the treatment of many other cancers. Each of them are individually licensed for the treatment of cancers such as advanced melanoma, non-small cell lung cancer, and bladder cancer in Australia. However, this treatment combination is experimental and is not approved to treat ovarian, fallopian tube or peritoneal cancers in any country.
- Cobimetinib is a drug that blocks a protein called Mitogen-activated protein kinase (MEK). MEK proteins are involved in the multiplication of cancer cells. By binding to the MEK protein, cobimetinib may help to stop the growth of cancer cells.
- Bevacizumab is an antibody (a type of protein produced by the immune system) that is specifically designed to block a protein called Vascular Endothelial Growth Factor (VEGF). VEGF is a protein that can increase the growth of tumour cells and binding to VEGF may help to stop the growth of tumours.
- Atezolizumab is a type of drug called a Programmed Cell Death Protein 1 (PD-L1) inhibitor. PD-L1 binds to PD-1 which is a type of protein found on the surface of cells in your body's immune system, and it controls the ability of your body's natural immune response to trigger the death of tumour cells. Tumour cells can hide from the immune system by using PD-L1, which stops your immune system from triggering tumour cell death. It is designed to block this PD-1/PD-L1 interaction by binding to PD-L1 so that PD-1 cannot bind to it and stops it from turning off your immune cells. This helps your immune system to recognise and destroy tumour cells. In turn, this potentially can stop or reverse the growth of your cancer.