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Senior Oncology Scientist: London Regional Cancer Program, London Health Sciences Centre
Assistant Director: Pamela Greenaway Kohlmeier Translational Breast Cancer Research Unit
Dentistry, Western University
Basic Science Co-Lead, Metastasis Translational Cancer Research Team: http://www.ctcr.ca/research/programs_metastasis.html
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
Cellular and Molecular Biology of Metastasis
Key Words: Breast cancer, prostate cancer, metastasis, circulating tumor cells, cancer stem cells, osteopontin, translational research
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, L.E., Lock, M., Rodrigues G., D'Souza, D., Bauman, G., Ahmad, B., Venkatesan, V., Allan, A.L., and Sexton, T. The significance of circulating tumor cells in prostate cancer patients undergoing adjuvant or salvage radiation. Prostate Cancer & Prostatic Diseases, 2015 Aug 4. doi: 10.1038/pcan.2015.36. PMID: 26238233 [Epub ahead of print].
Mohamadi, R.M., Besant, J.D., Mepham, A., Mahmoudian, L., Gibbs, T., Ivanov, I., Malvea, A., Stojcic, J., Allan, A.L., Lowes, L.E., Sargent, E.H., Nam, R.K., and Kelley, S.O. Nanoparticle-mediated binning and profiling of heterogeneous circulating tumor cell subpopulations. Angewandte Chemie, 2015 54(1):139-43.
Lowes LE, Goodale D, Xia Y, Postenka C, Piaseczny MM, Paczkowski F, Allan AL. Epithelial-to-mesenchymal transition leads to disease-stage differences in circulating tumor cell detection and metastasis in pre-clinical models of prostate cancer. Oncotarget. 2016;7(46):76125-76139.
Lowes LE, Bratman SV, Dittamore R, Done S, Kelley SO, Mai S, Morin RD, Wyatt AW, Allan AL. Circulating Tumor Cells (CTC) and Cell-Free DNA (cfDNA) Workshop 2016: Scientific Opportunities and Logistics for Cancer Clinical Trial Incorporation. Int J Mol Sci. 2016;17(9). pii: E1505.
Connor AA, McNamara K, Al-Sukhni E, Diskin J, Chan D, Ash C, Lowes LE, Allan AL, Zogopoulos G, Moulton CA, Gallinger S. Central, But Not Peripheral, Circulating Tumor Cells are Prognostic in Patients Undergoing Resection of Colorectal Cancer Liver Metastases. Ann Surg Oncol. 2016;23(7):2168-75.
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
Chu, J.E.*, Xia, Y.*, Chin-Yee, B., Goodale, D., Croker, A.K., and Allan A.L. Lung-derived factors mediate breast cancer cell migration via CD44 receptor-ligand interactions in a novel ex vivo system for analysis of organ-specific soluble proteins. Neoplasia, 2014, 16 (2): 180-191. *These two authors contributed equally to this manuscript.
Piaseczny, M., and Allan, A.L. Why does breast cancer often spread to the lung? Womens Health (Lond Engl), 2014;10(6):561-564.
Rodriguez-Torres M, Allan AL. Aldehyde dehydrogenase as a marker and functional mediator of metastasis in solid tumors. Clin Exp Metastasis. 2016;33(1):97-113.
Piaseczny MM, Pio GM, Chu JE, Xia Y, Nguyen K, Goodale D, Allan A. Generation of Organ-conditioned Media and Applications for Studying Organ-specific Influences on Breast Cancer Metastatic Behavior. J Vis Exp. 2016;(112).
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
Lori Lowes, Postdoctoral Research Associate
Project: Molecular characterization of circulating tumor cells in breast and prostate cancer
Ashkan Sadri, MSc Graduate Student (Dept. of Anatomy & Cell Biology)
Project: Functional role of soluble and ECM factors lung-derived factors on supporting and/or promoting the breast cancer stem cell phenotype.
Sami Khan, MSc Graduate Student (Dept. of Anatomy & Cell Biology)
Project: CD44 receptor-ligand interactions and their involvement in breast cancer metastasis to the lung.
Jenna Kitz, MSc Graduate Student (Dept. of Anatomy & Cell Biology)
Project: Dynamic influence of the epithelial-to-mesenchymal transition on circulating tumor cell (CTC) generation, phenotype, and progression to metastasis in prostate cancer.
Cory Lefebvre, MD/PhD Graduate Student (Dept. of Anatomy & Cell Biology)
Project: Kinome profiling of triple negative breast cancer in response to targeted therapy.
Michael Keeney, ART, FIMLS
Hematology/Flow Cytometry, London Health Sciences Centre; and Lawson Health Research Institute
David Hess, PhD
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, PhD
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, PhD
Department of Pathology and Molecular Medicine, Kingston General Hospital and Queen’s University; and National Cancer Institute of Canada Clinical Trials Group
Profile of Excellence, Schulich School of Medicine & Dentistry:
What's Your Why?:
Western News, September 24, 2015: Research looks to deny cancer fertile ground in lungs: http://news.westernu.ca/2015/09/research-looks-to-deny-cancer-fertile-ground-in-lungs/
CTV2 London News, August 24, 2015: Breast cancer research gets a big boost. http://london.ctvnews.ca/video?clipId=687461.