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Oncology Scientist, London Regional Cancer Program, London Health Sciences Centre
Assistant Director: Pamela Greenaway Kohlmeier Translational Breast Cancer Research Unit
Cross-Appointments: Associate Professor, Departments of Oncology and Anatomy & Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario
Cancer Research Laboratory Program
London Regional Cancer Program, London Health Sciences Centre
Victoria Research Labs, Room A4-132
Canada N6A 4L6
Tel: 519.685.8600 Ext. 55134
University website: http://www.uwo.ca/anatomy/department/allana/aallan.html
Cellular and molecular biology of metastasis
Key Words: Breast cancer, prostate cancer, metastasis, circulating tumor cells, cancer stem cells, osteopontin, translational research
Ying Xia, Postdoctoral Research Associate
Project: Single Cell analysis of heterogeneous circulating tumor cells and cancer stem cells
David Goodale, Research Technician
Project: Detection and analysis of circulating tumor cells in mouse models of breast cancer
Alysha Croker, PhD Graduate Student (Dept. of Anatomy & Cell Biology)
Project: Role cancer stem cells in breast cancer metastasis and treatment
Lori Lowes, PhD Graduate Student (Dept. of Anatomy & Cell Biology)
Project: Molecular characterization of circulating tumor cells in breast and prostate cancer
Mauricio Rodriguez Torres, PhD Graduate Student (Dept. of Anatomy & Cell Biology)
Project: Role of tumor-derived stem cell factors in the organ tropism of breast cancer metastasis
Graciella Pio, 4th Year Undergraduate Honours Research Student
Project: Role of bone-derived factors in the organ tropism of breast cancer metastasis
Dr. Allan’s research interests lie in the study of molecular mechanisms that influence normal cellular growth, tumor development, and cancer progression. The focus of Dr. Allan’s research program is cancer metastasis and translational research. Despite the fact that the majority of deaths from solid cancer occur due to the physiological effects of metastasis rather than from the consequences of the primary tumor, metastasis remains a badly understudied field. A major area of research that is needed to address this problem involves gaining a greater understanding of the metastatic process as a whole, such that current therapies can be better utilized to target metastatic disease, and new, more effective therapies can be developed which will better treat or prevent cancer metastasis. A second important area of research is the identification and development of surrogate marker approaches that will allow close monitoring of both disease progression and response to therapy. Dr. Allan’s research program encompasses both of these areas, and involves two individual but interrelated projects.
1. Clinical and biological importance of circulating tumor cells (CTCs) in cancer patients and mouse models of metastasis:
Clinical studies have shown that rare disseminated tumor cells in the peripheral bloodstream or bone marrow of patients with breast and other cancers may be an important indicator of the potential for metastatic disease and poor prognosis. However, the biological implications of these cells remain poorly understood, particularly with regards to the functional and mechanistic details of their progression to clinically relevant metastases. Our lab has established novel and sensitive methods to identify and characterize rare disseminated tumor cells in the blood, bone marrow, and distant organ sites in mouse models of human breast cancer, as well as in the peripheral blood of cancer patients. These studies are helping us elucidate the mechanistic details of early steps in metastasis and how these steps relate to the development of life-threatening metastases in animal models and patients. In addition, these methods will be extremely valuable for the future identification, development, and testing of new therapeutic strategies to combat breast and other cancers.
Recent Publications in this Area
Lowes LE, Hedley BD, Keeney M, Allan AL. User-defined protein marker assay development for characterization of circulating tumor cells using the CellSearch® system. Cytometry A. 2012 Aug 16. doi: 10.1002/cyto.a.22158. [Epub ahead of print] PMID: 22899576.
Lowes, L.E., Lock. M., Rodrigues, G., D’Souza, D., Bauman, G., Venkatesan, V., Allan, A.L., and Sexton, T. Circulating tumor cell analysis in prostate cancer patients receiving salvage radiotherapy. Clin Transl Oncol. 2012 Feb;14(2):150-6.
Nichols A.C., Lowes, L.E., Szeto, C.C.T., Basmaji, J., Dhaliwal, S., Chapeskie, C., Todorov, B., Read, N., Venkatesan, V., Hammond, A., Palma, D.A., Winquist, E., Ernst, S., Fung, K. Franklin, J.H., Yoo, J., Koropatnick, J., Mymryk, J.S., Barrett, J.W., Allan, A.L. Detection of circulating tumor cells in advanced head and neck cancer using the CellSearch® system. Head Neck, 2011 Nov 11. doi: 10.1002/hed.21941. [Epub ahead of print; PMID: 22076949].
Lowes LE, Goodale D, Keeney M, Allan AL. Image cytometry analysis of circulating tumor cells. Methods Cell Biol. 2011;102:261-90.
2. Role of cancer stem cells in breast cancer metastasis and treatment:
Metastasis is an inefficient process, such that very few cells that leave a tumor successfully form macrometastases in distant sites. This, coupled with the inherently heterogeneous nature of the cancer cell population within solid tumors, suggests that only a small subpopulation of cells can successfully initiate tumor growth and navigate the metastatic cascade to eventually form life-threatening metastases in distant organs. We hypothesize that this rare subpopulation of cells are in fact cancer stem cells (CSCs). Recent experimental studies in our lab indicate that breast cancer cells with a "stem-like" phenotype display enhanced adhesion, migration, invasion, metastasis, and therapy resistance. In collaboration with the LHSC Divisions of Surgery, Oncology, and Hematology, our lab has also undertaken translational studies aimed at characterizing breast cancer CSCs in patient samples, including assessment of the role that CSCs play in patient response to chemotherapy and radiation treatment. Taken together, these novel studies will allow us to answer a number of important and previously uninvestigated questions regarding the role of CSCs in breast cancer metastasis and treatment. Although some early stage cancers can be successfully treated by surgery, radiation, and/or chemotherapy, the majority of current therapies fail in the metastatic setting. Therefore, our consideration of the CSC hypothesis in the context of metastasis and response to therapy could have far-reaching implications to the way that we not only study cancer, but more importantly how we treat it.
Recent Publications in this Area
Croker A.K. and Allan A.L. Inhibition of aldehyde dehydrogenase (ALDH) reduces chemotherapy and radiation resistance of stem-like ALDHhiCD44+ breast cancer cells. Breast Cancer Res Treat. 2012;133(1):75-87.
Chu, J.E. and Allan, A.L. The role of cancer stem cells in the organ tropism of breast cancer metastasis: a balance between the “seed” and the “soil?” Int J Breast Cancer. 2012;2012:209748.
Ma I, Allan AL. The role of human aldehyde dehydrogenase in normal and cancer stem cells. Stem Cell Rev. 2011 Jun;7(2):292-306.
Croker, A.K., Goodale, D., Chu, J., Postenka, C., Hedley, B.D., Hess, D.A., and Allan, A.L. High aldehyde dehydrogenase activity and expression of cancer stem cell markers selects for stem-like breast cancer cells with enhanced malignant and metastatic properties. J Cell Mol Med. 2009, 13(8b), 2236-2252.
Michael Keeney, ART, FIMLS
Hematology/Flow Cytometry, London Health Sciences Centre; and Lawson Health Research Institute
David Hess, Ph.D.
Stem Cell Biology, Robarts Research Institute
Anargyros Xenocostas, MD, FRCPC
Hematology, London Health Sciences Centre; and Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario
Tracy Sexton, MD, PhD, FRCPC
Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre; and Departments of Oncology and Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario
Michael Lock, MD, CCFP, FRCPC
Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre; and Department of Oncology, Schulich School of Medicine and Dentistry, University of Western Ontario
Muriel Brackstone, MSc, MD, FRCPC
Surgical Oncology, London Regional Cancer Program, London Health Sciences Centre; and Departments of Surgery and Oncology, Schulich School of Medicine and Dentistry, University of Western Ontario
Ann F. Chambers, Ph.D.
Cancer Research, London Regional Cancer Program, London Health Sciences Centre; and Departments of Oncology, Medical Biophysics, Pathology, and Microbiology & Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario
Jeremy Squire, Ph.D.
Department of Pathology and Molecular Medicine, Kingston General Hospital and Queen’s University; and National Cancer Institute of Canada Clinical Trials Group