Improved response to drug therapy for cancer
Dr Simpson has discovered that drugs that trap and cluster the Epidermal Growth Factor Receptor (EGFR) on the cell surface dramatically improve the capacity of the immune system to kill tumour cells following Cetuximab therapy. Critically, tumour cells previously resistant to Cetuximab therapy now become destroyed by the immune system. These drugs include anti-psychotics already in use in the clinic. The opportunity to repurpose these drugs presents a rapid entry point for clinical trials designed to improve patient response rates to Cetuximab and also to other ADCC inducing antibodies in other cancers (eg Traztuzamab in breast cancer).
| Head Researcher | Dr Fiona Simpson |
|---|---|
| Team Members |
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| Body Part | Head and Neck |
| Equipment Used | 3D-SIM microscopy, multi-variant Facs, tumour live ex vivo imaging |
| Process Used | Monitored trafficking of the EGFR through live patient-derived tumour biopsies |
| Research Areas | Immunology |
| Disease | Cancer, Head and Neck squamous cell carcinoma, Breast Cancer |
| Tags | Cellular trafficking, Epidermal Growth Factor Receptor Family |
| Commercial Partnerships | Undisclosed commercial backing |
| Institutions | University of Queensland, University of Newcastle, University of Sydney, Children’s Medical Research Institute (Sydney) |
About the Project
Dr Simpson is an expert in the cellular trafficking of the Epidermal Growth Factor Receptor (EGFR). The EGFR is commonly over-expressed in cancers such as head and neck squamous cell carcinoma (SCC), to the extent that an antibody that targets the EGFR (cetuximab) is commonly used as a therapy in the clinic. However, despite the over expression of EGFR in most patients, this antibody is effective in less than 30% of patients, in which progression-free survival is greatly improved. Until now however, no one knew why.
Dr Simpson developed a method that allows her to monitor the trafficking of the EGFR through live patient-derived tumour biopsies. Using this method, she discovered that the position and clustering of the EGFR on the cell surface determines the therapeutic response to therapy – in essence, those patients in which the EGFR is held and clustered at the cell surface are the same patients that respond to Cetuximab therapy.
Following on from that discovery, and with the help of her team, she has determined that clustering of the EGFR on the cell surface is critical for Cetuximab to activate the immune system and result in tumour cell killing. Consequently, Dr Simpson has discovered that drugs that trap and cluster the EGFR on the cell surface dramatically improve the capacity of the immune system to kill tumour cells following Cetuximab therapy, and critically, that tumour cells previously resistant to Cetuximab therapy now become destroyed by the immune system. These drugs include anti-psychotics already in use in the clinic. The opportunity to repurpose these drugs presents a rapid entry point for clinical trials designed to improve patient response rates to Cetuximab. Using breast cancer cells the combination therapy was shown to be effective in both increasing traztuzamab-mediated killing of Her2 positive breast cancer and effective in Cetuximab-mediated killing of EGFR positive triple negative breast cancers.
Translational Research - Milestone T3
Dr Fiona Simpson and her team are undertaking a clinical trial to test drugs such as Stemetil in combination with Cetuximab at the Princess Alexandra Hospital (PAH) for any improvement they may make to patient response rates. In future the team wish to expand these trials to the improvement of other monoclonal antibody therapies, especially in triple negative and in Her2 positive breast cancers. The team are also involved in the development of “on-target” inhibitors to increase efficiency over the currently tested inhibitors.
>For commercial partnership opportunities, please contact Maher Khaled [email protected] at UQ'S COMMERCIAL PARTNER, UNIQUEST.
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Head Researcher Dr Fiona Simpson
