Ann Chambers
Adjunct Professor, Medical Biophysics
PhD
Office: LHSC VH A4-903B (LRCP)
Phone: (519) 685-8652
E-mail: ann.chambers@lhsc.on.ca
Research Activities
Keywords: Biology and regulation of metastasis, tumor progression and dormancy
Description of research activities:
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.
