Real Research

2020 Funded Breast Cancer Research Projects

Thanks to the funds raised through Project Pink, The PA Research Foundation has been able to commit funding to several groundbreaking breast cancer research projects in 2020. Two of these projects include:

Project: Increasing the number of breast cancer therapeutic antibody possibilities, patient choices and success rates

Lead investigator: Dr Shannon Joseph. Collaborative project team: F Simpson, K cuff, B Panizza, E Walpole

Project Summary

A number of pharma companies have developed breast cancer therapies called 'monoclonal antibodies'. Despite the science behind the technology being excellent, and some antibodies reaching Phase III trials, the efficiency was not high enough to replace current therapies. That's millions of dollars spent for no better treatment for breast cancer patients. Our aim is to rescue some of the technology. Our laboratory has recently found a way to enhance responses in targeted antibody therapy. This works by inhibiting a molecule called dynamin that results in trapping the drug target on the tumour cell surface, causing more efficient binding of the treatment antibody and recruitment of immune cells that increases tumour cell killing.

Our Phase I clinical trial using this combination therapy has so far been safe. We tested whether we could improve antibodies previously developed but not current therapies. We have shown that we can enhance antibody therapies whose target enters cells via dynamin pathways, but not monoclonal antibody therapies that aren't internalised that way. Using experimental models we have analysed how the combination drug is metabolised in the body and shown it is reversible and specific. Together this data will be used to inform drug combination therapies to enable better design of patient treatments in our Phase II clinical trial.

Research Benefits

1/10 women, and an increasing number of men in the Western world develop breast cancer. The incidences keep increasing. Conventional anti-hormonal and chemotherapy have severe side-effects and are not sufficient to cure or stabilise the disease in every patient. We have shown that we can increase the efficiency of a targeted cancer drug (cetuximab) and we aim to apply this strategy to alternative antibody therapies for breast cancer treatment. This technology has the potential to improve treatment for Her2- positive and Triple negative breast cancer.

Project: Mammographic Density (MD) as a modifiable breast cancer risk factor and indicator of response to therapy

Lead investigator: Prof Erik Thompson. Collaborative project team: H Hugo, T Lloyd, C Snell, K Momot, G Santamaria

Prof Rik Thompson and Dr Honor Hugo

Project Summary

Mammographic Density (MD) corresponds to the white area on a mammogram. It is a risk factor for breast cancer (BC) and can also interfere with mammogram efficiency. Our studies of high MD regions in breast tissues have led to a focus on a set of molecules called Syndecans. We are analysing their regulation, their inhibition, and their levels in the blood. In a world-first, our PA Research Foundation-supported studies have accurately quantified MD in excised breast tissue and now reliably in human subjects, using a novel Portable NMR instrument, paving the way forward for clinical application.

Areas of high MD have dense connective tissue around the mammary glands (fibroglandular tissue). We have examined the genes and proteins of this tissue, cultured breast tissue from high MD regions to study responses to various factors, and measured shed MD-associated proteins in serum. We have focussed in on a set of molecules (Syndecans) and analyse their regulation, inhibition, and levels in the blood.

Several Portable NMR measurements were compared with MD measurements obtained by mammography with quantitative agreement. This enables us to quantify the relative contents of different tissue types (e.g. fat and fibroglandular tissue) within breast tissue samples, and we have conducted a trial to test this instrument for the measurement of MD in the body ("in vivo"). We found the approach to be feasible and provides a safe, noninvasive way of measuring MD within the breast. We also found a good agreement between tissue composition profiles obtained from Portable NMR and clinical "gold standard" MRI. The approach shows great promise for safe and accurate clinical mammographic imaging, and we now plan to optimise this for repeat sampling and test whether we can detect reductions in MD in women receiving hormonal therapy for BC.

Research Benefits

Understanding the reasons that MD is a risk factor has potential to improve our efforts to prevent, detect and treat breast cancer (BC). Our pathobiology studies address this. Almost 70% of all breast cancers are hormone-receptor positive, where hormone therapies are administered but will not benefit the patient in about 1/3 of the women treated. Identifying such non-responders would be ideal, as they can avoid possible side-effects and/or switch to other therapies. Our Portable NMR may allow monitoring of response to hormonal therapies in BC, and could lead to improvements in BC management.

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