Distinguished Oncology Scientist: London Regional Cancer Program, London Health Sciences Centre, London, Ontario
Canada Research Chair in Oncology: Canada Research Chairs
Professor of Oncology: University of Western Ontario, London, Ontario
London Regional Cancer Program
Cancer Research Laboratory Program
790 Commissioners Rd. E.
Canada N6A 4L6
Biology and regulation of metastasis, tumor progression and dormancy
Summary of Current Work
Metastasis, Dormancy and Late Recurrence: Metastasis, the spread of cancer cells from a primary tumor to new sites, is a major factor in preventing successful treatment of cancer. Metastasis can occur after years of dormancy following treatment of a primary cancer. We are using experimental and clinical approaches to study mechanisms that regulate metastasis and tumor dormancy. We learned that large numbers of dormant single cells may remain in secondary organs, with the potential to resume growth at later times to form metastases. These cells are resistant to cytotoxic chemotherapies that target dividing cells. We are working identifying vulnerabilities in dormant cells and new ways to target them therapeutically. We are using in vitro models to study the molecular regulation of tumor dormancy. We are collaborating with Drs. Paula Foster and John Ronald to use novel cellular magnetic resonance and molecular imaging approaches to study metastasis and tumor dormancy. In collaboration with Dr. Jim Lacefield, we are using small animal ultrasound approaches to quantify and model tumor growth and blood flow parameters. We are collaborating with Dr. Eugene Wong to develop new microfluidic devices to study interactions between cancer cells and their tissue microenvironment.
Osteopontin as a Biomarker and Regulator of Cancer Aggressiveness: We are studying how an oncogene-induced, integrin-binding protein called osteopontin (OPN) contributes to the growth and progression of breast and other tumors, in collaboration with Dr. Alan Tuck. We showed that OPN promotes malignancy of cells in culture, and we are studying how OPN affects tumor growth, progression and responses to targeted therapies. We developed an ELISA to measure OPN plasma levels in patients and in clinical studies, we learned that women with metastatic breast cancer, as well as men with castrate resistant prostate cancer, have elevated blood OPN levels. OPN tissue levels are also elevated in tumor types. We found that elevated OPN levels in blood or tumor tissue are associated with poorer survival. These experimental and clinical studies will clarify the role of OPN functionally in cancer, and its potential role as a prognostic and predictive biomarker in breast, prostate and other cancers.
Early Breast Cancer Progression: In collaboration with Dr. Tuck, we also are studying molecular determinants of early breast cancer progression. Using in vitro and in vivo models, we have identified a series of genes whose expression changes as breast cells progress from atypical ductal hyperplasia, to ductal carcinoma in situ, to invasive mammary carcinoma. These biomarkers may help in determining the potential aggressiveness of early breast lesions, and refine treatment strategies for these patients.
The overall aim of our research is to learn how cancer cells spread, how they can become dormant and what triggers their awakening, in order that new approaches to prevent, delay or treat metastatic disease and late recurrences can be developed.
Brackstone M, Palma D, Tuck AB, Scott L, Potvin K, Vandenberg T, Perera F, D'Souza D, Taves D, Kornecki A, Muscedere G, Chambers AF. 2017. Concurrent neoadjuvant chemotherapy and radiation therapy in locally advanced breast cancer. International Journal of Radiation Oncology Biology Physics doi.org/10.1016/j.ijrobp.2017.06.005 View Publication (PDF)V
Kirstein JM, Hague MN, McGowan PM, Tuck AB, Chambers AF. 2016. Primary melanoma tumor inhibits metastasis through alterations in systemic hemostasis. Journal of Molecular Medicine 94:899-910. View Publication (PDF) V
Barkan D, Chambers AF. 2016. Prevention of conversion of tumor dormancy into proliferative metastases. In: Cote R, Datar R (editors), Circulating Tumor Cells, Springer. Chapter 7, pp 121-137.View Publication (PDF)
Allan AL, Chambers AF. 2016. Circulating tumor cells and tumor dormancy. In: Cote R, Datar R (editors), Circulating Tumor Cells, Springer. Chapter 6, pp 101-120. View Publication (PDF)
Chambers AF, Werb Z. 2015. Invasion and metastasis – Recent advances and future challenges, Journal of Molecular Medicine 93:361-368. View Publication (PDF)
Zarghami N, Jensen MD, Talluri S, Foster PJ, Chambers AF, Dick FA, Wong E. 2015. Technical Note: Immunohistochemical evaluation of mouse brain irradiation targeting accuracy with 3D-printed immobilization device. Medical Physics 42:6507-13. doi: 10.1118/1.4933200. View Publication (PDF)
Bramwell VH, Tuck AB, Chapman JA, Anborgh PH, Postenka CO, Al-Katib W, Shepherd LE, Han L, Wilson CF, Pritchard KI, Pollak MN, Chambers AF. Assessment of osteopontin in early breast cancer: correlative study in a randomised clinical trial. Breast Cancer Res. 2014 Jan 22;16(1):R8. doi: 10.1186/bcr3600. View Publication (PDF)
Barkan D, Chambers AF. 2011. β1-integrin: A potential therapeutic target in the battle against cancer recurrence. Clinical Cancer Research 17:7219-23.
Goss PE, Chambers AF. 2010. Does tumour dormancy offer a therapeutic target? Nature Reviews Cancer 10: 871-877, 2010.
Townson JL, Ramadan SS, Simedrea C, Rutt BK, MacDonald IC, Foster PJ, Chambers AF. 2009. Three-dimensional imaging and quantification of both solitary cells and metastases in whole mouse liver by magnetic resonance imaging. Cancer Research 69: 8326-8331.
Anborgh PH, Wilson SM, Tuck AB, Winquist E, Schmidt N, Hart R, Maeda M, Kon S, Uede T, Stitt LW, Chambers AF. 2009. New dual monoclonal ELISA for measuring plasma osteopontin as a biomarker associated with survival in prostate cancer: clinical validation and comparison of multiple ELISAs. Clinical Chemistry 55: 895-903.
Heyn C, Ronald JA, MacKenzie LT, MacDonald IC, Chambers AF, Rutt BK, Foster PJ. 2006. In vivo magnetic resonance imaging of single cells in mouse brain with optical validation. Magnetic Resonance in Medicine 55: 23-29.
Bramwell VHC, Doig GS, Tuck AB, Wilson SM, Tonkin KS, Tomiak A, Perera F, Vandenberg TA, Chambers AF. 2006. Serial plasma osteopontin levels have prognostic value in metastatic breast cancer. Clinical Cancer Research 12: 3337-3343.
Rittling SR, Chambers AF. 2004. Role of osteopontin in tumor progression. British Journal of Cancer 90: 1877-1881.
Coppola D, Szabo M, Bouleware D, Muraca P, Alsarraj M, Chambers AF, Yeatman TJ. 2004. Correlation of OPN protein expression and pathologic stage across a wide variety of tumor histologies. Clinical Cancer Research 10: 184-190.
Naumov GN, Townson JL, MacDonald IC, Wilson SM, Bramwell VHC, Groom AC, Chambers AF. 2003. Ineffectiveness of doxorubicin treatment on solitary dormant mammary carcinoma cells or late-developing metastases. Breast Cancer Research and Treatment 82: 199-206.
Chambers AF, AC Groom and IC MacDonald. 2002. Dissemination and growth of cancer cells in metastatic sites. Nature Reviews Cancer 2: 563-572, 2002.
Naumov GN, MacDonald IC, Weinmeister PM, Kerkvliet N, Nadkarni KV, Wilson SM, Morris VL, Groom AC, Chambers AF. 2002. Persistence of solitary mammary carcinoma cells in a secondary site: a possible contributor to dormancy. Cancer Research 62: 2162-2168.
Chambers AF, Matrisian LM. 1997. Changing views of the role of matrix metalloproteinases in metastasis. Journal of the National Cancer Institute 89: 1260-1270.
Singhal H, Bautista DS, Tonkin KS, O’Malley FP, Tuck AB, Chambers AF, Harris JF. 1997. Elevated plasma osteopontin in metastatic breast cancer associated with increased tumor burden and decreased survival. Clinical Cancer Research 3: 605-611.
David Holzman. 1996. New view of metastasis is spreading. Journal of the National Cancer Institute 88:1336-1338.
Jocelyn Rice. Metastasis: The rude awakening. Nature 485, S55–S57 (31 May 2012)
Alan B. Tuck, MD, PhD, FRCPC (Anatomic Pathology)
Departments of Pathology and Oncology, University of Western Ontario
Staff Pathologist: Department of Pathology
Paula Foster http://www.robarts.ca/paula-foster
Robarts Research Institute, University of Western Ontario
John Ronald http://www.robarts.ca/john-ronald
Robarts Research Institute, University of Western Ontario
James Lacefield http://www.eng.uwo.ca/people/jlacefield
Department of Electrical and Computer Engineering, University of Western Ont
Eugene Wong http://www.physics.uwo.ca/~ewong
Department of Physics and Astronomy, University of Western Ontario
Staff and Research Trainees
Pieter Anborgh, PhD
Project: Experimental and clinical studies on the role of osteopontin in cancer
Email: Dr. Pieter Anborgh
PhD student, Pathology and Laboratory Medicine Department
Supervisor: Dr. Alan Tuck
Joint Supervisor: Dr. Ann Chambers
Project: Role of the transcriptional regulator TBX3 in early breast cancer progression
Email: Milica Krstic
MSc student, Physics and Astronomy Department
Supervisor: Dr. Eugene Wong
Joint Supervisor: Dr. Ann Chambers
Project: Design, fabrication and evaluation of microfluidic devices for the study of breast cancer metastasis
Email: David Uren
David Dales, BSc (Honours Genetics), Senior Research Technician
Specialty: Molecular and cellular biology and overall laboratory management
Email David Dales
Nicole Hague, BSc, RVT
Specialty: Veterinary technician
Email Nicole Hague
Carl Postenka, BSc, M.L.T., Histology Research Technician
Specialty: Animal handling and all aspects of histology (with Dr. Alan Tuck)
Email Carl Postenka
Joseph Andrews, Bsc, MSc, Research Technician
Specialty: Microarray technology, molecular biology;
bioinformatics (with Dr. David Rodenhiser)