Peter MacCallum Cancer Centre
Presentation Title
Regulation of breast cancer metastasis
Abstract
About 2,700 deaths from breast cancer occur in Australia each year and in 2010, breast cancer accounted for 40,600 years of life lost due to premature deaths. Nearly all these deaths are due to the onset of metastatic disease. So far, we have had very little success in preventing the mortality associated with metastatic disease, with therapies either being palliative or treating a single lesion in a secondary tissue. A therapy that is successful in eradicating metastatic disease or in preventing growth of micrometastases would therefore have enormous impact on breast cancer morbidity and mortality.
Breast cancer metastases have a strong avidity for liver, lungs, brain and bone. A significant fraction of breast cancer patients have micro-metastatic disease at diagnosis, which can develop into clinically relevant lesions after a latency of 5-20 years and become refractory to current therapies. Despite many years of research into metastasis, the molecular events underlying the escape of metastatic cells from primary tumours and their spread to specific tissues are not fully understood. A number of genes that can be classified as either metastasis promoters or suppressors have been identified, but it is evident that these give only a partial view of the metastatic process at a molecular level.
Our research is focussed on the use of clinically relevant mouse models of metastatic breast cancer from which we can identify genes associated with the ability to metastasise. These models can also be used to demonstrate that the gene has a regulatory role in metastasis. A final confirmation of the relevance of the identified gene comes from analyses of cohorts of human breast cancer samples, linking the expression of the gene with clinical outcome.
Some examples of genes that we have found to be associated with metastatic disease in patients include laminin-511, caveolin-1, cathepsin B and BMP4. Of particular note, all these genes are involved in tumour–stromal interactions, highlighting the role of host tissues in the metastatic process.
Biographical
Robin Anderson completed an honours degree in Agricultural Science at The University of Melbourne before embarking a PhD in biochemistry at La Trobe University. The next 15 years were spent overseas, first at Stanford University, at the MRC Cyclotron Unit in London followed by a second stint at Stanford University. It was during the first postdoctoral fellowship at Stanford where she switched from plant biochemistry to oncology. Since returning to Melbourne, she has focussed on the regulation of metastasis, with emphasis on breast cancer. Her interests are in developing clinically valid mouse models of metastatic disease to allow identification of the genes that regulate metastasis and to develop molecular targeted therapies for advanced cancer.
She is currently a Principal Research Fellow at the Peter MacCallum Cancer Centre, a Senior Research Fellow of the National Breast Cancer Foundation, honorary Associate Professor at The University of Melbourne and Editor of the journal Clinical & Experimental Metastasis.
Research Overview
The Metastasis Research Laboratory studies the process of metastasis — the spread of cancer to other sites — which is the main cause of morbidity for patients with solid cancers. Whilst therapy for primary tumours is often effective, there are few treatment options for patients whose tumours have spread to other organs. It is our overall aim to identify the key genes that regulate the process of metastasis, expressed by either the tumour cells or by surrounding host cells. From this information, compounds that specifically target these gene products can be identified and tested for their potential to block the process of metastasis, initially in preclinical models, and later in patients.
To progress these studies, we have developed clinically relevant models of metastatic disease in mice, primarily for breast cancer, but also for colon cancer. We are further refining these models to study metastasis to specific sites such as bone, liver or brain. From our genomic profiling of the primary tumours and their metastases in various organs, we have identified genes critical to the process of metastasis. These genes are potential targets for development of new molecular based therapies for advanced cancer and/or are useful prognostic markers of disease progression. Our current studies are aimed at understanding how these genes regulate metastasis and focused on developing compounds to inhibit their activity.
Further Information
Metastasis Research Laboratory
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