There are about 100 people working on breast cancer research at the BC Cancer Agency and with collaborating groups at the University of British Columbia and Dr. Samuel Aparicio is at the helm. Head of the Department of Breast and Molecular Oncology at the BC Cancer Research Centre, he is also Department Head and a Professor of Pathology and Laboratory Medicine at UBC, Associate Member of Medical Genetics at UBC, and holds the Nan and Lorraine Robertson Chair in Breast Cancer Research. He joined the BC Cancer Agency in 2005 having previously worked in the Department of Oncology at the University of Cambridge.
Dr. Aparicio shares his insight here into the key areas of his research.
Complementary Research Themes
My team at the BC Cancer Research Centre is engaged in a number of complementary research projects that focus on the molecular characterisation of normal and cancerous breast cells. We also work in collaboration with colleagues at BCCA regional centres, at other Canadian institutions and elsewhere.
A primary focus is the molecular techniques which name and classify breast cancer. We have a collaborative project between Canada and the United Kingdom, now in the pilot phase, that is aiming to classify breast cancer tumours into categories and subcategories beyond which they are presently defined and treated. The goal is to identify novel molecules that can help physicians make better decisions about individuals cancer treatment.
Toward this end, we are beginning an analysis of 2,000 archived tumour biopsies using a range of techniques to characterise each tissue sample. We will be able to determine, for example, whether any chromosome segments are absent or amplified in the tumour cells. The genes that are expressed or activated in each cell will also be compared, and the presence of mutations in genes that are commonly damaged in breast cancer cells will be assessed. Detailed, anonymous clinical information is available for each sample such as what each patient received, how they responded and so on. This enables researchers to correlate the molecular make-up of each sample with patients medical history.
Another research focus involves screening the human genome for genes involved in breast cancer. Using RNA interference technology, this technique enables us to rapidly identify genes and proteins that interact with molecules already known to play a role in breast cancer. Every new interaction partner that we discover has the potential to be targeted by new chemotherapy drugs.
We can detect genes, for example, that are involved in repairing damaged DNA in breast cancer cells. There are multiple repair mechanisms that operate in human cells, and whole-genome screening allows us to sort the relevant genes into their different pathways. Genes that are in the same pathway have similar effects on the cell when repressed, and disabling two genes in the same pathway will have a similar effect to repressing any single gene. In contrast, disabling two genes that belong to different pathways will cause a more severe effect than repressing either gene alone. It is therefore possible to determine whether two genes are in the same or different pathways.
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The third common research theme in my laboratory is the study of mammary stem cells. In early 2006, stem cells were identified in the mouse mammary gland. This was an important discovery that also implicated mammary epithelial stem cells in the development of breast cancer. The idea that stem cells are involved in cancer has significant implications for cancer therapy, particularly with regards to drug resistance. Stem cells often express drug-resistance proteins and high levels of proteins that block apoptosis (cell death). If cancer stem cells can be forced to differentiate, they would lose this drug resistance and become more sensitive to chemotherapy. Thoroughly characterizing normal mammary stem cells will allow us to determine what processes encourage differentiation, with the hope of triggering this pathway in cancer stem cells. Additionally, basic information regarding the factors that govern the growth and differentiation of normal stem cells will allow us to determine what drives malignant transformation and provide clues into how to prevent cancer initiation.
My laboratory is using the whole-genome screening techniques described above to identify genes that are involved in the proliferation of epithelial stem cells, and in their differentiation into other cell types. We are also investigating how proteins interact during these processes, focusing initially on several proteins that are known to play a role in breast cancer. Other lab members are also working on methods that will improve the efficiency of mouse mammary stem cell isolation.
For those interested in keeping up to the date on our research initiatives, I would encourage you to view the BC Cancer Agencys website at www.bccancer.bc.ca or visit the BC Cancer Research Centres website at www.bccrc.ca.
The Weekend to End Breast Cancer
Finally, I would like to encourage readers to take part in this years Weekend to End Breast Cancer, September 5 7 in Vancouver benefiting the BC Cancer Foundation (www.endcancer.ca). A great deal of our work is supported by this fabulous event and in fact, their support was the single biggest factor in my decision to come to Vancouver. My family and I will be walking our 60km for the fourth year now and I invite others to join us.
A strong supporter of The Weekend to End Breast Cancer (Sept.5 7), Dr. Aparicio is shown here with his walking team: wife Dr. Catriona Aparicio, a member of the BCCAs palliative care program, and their four daughters.
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