Translational Research/Experimental Therapeutics in Cancer
McGill Centre for Translational Research in Cancer/Montreal Centre for Experimental Therapeutics in Cancer (MCTRC/MCETC)
Director: Gerald Batist, MD
Administrative Assistant: Angela Fragomene
Administrative Coordinator: Annie Rompré, MSc(A)
Research Coordinator: Miriam Santos Dutra, PhD
The great challenge faced by the oncology research community is in the translation of laboratory and clinical research data into clinical outcomes of benefit in the assessment, treatment and prevention of cancer. The McGill Centre for Translational Research in Cancer (MCTRC) was established in 1996, thanks to a generous endowment gift from the Goldfarb Family Foundation and the Alexander Family Foundation. Subsequent significant support included an endowment gift from the Montreal Breast Cancer Foundation. A 1997 article in the McGill Reporter outlines the origins of the McGill Centre for Translational Research in Cancer.
Based at the Sir Mortimer B. Davis-Jewish General Hospital/Lady Davis Institute, the Centre provides the infrastructure to bring the investigators involved in "translational research" together to generate novel approaches to cancer treatment and adds a key element to the coordination of cancer researchers by providing a structured focus for these activities. At its inception, the Centre included members from the McGill Departments of Anatomy & Cell Biology, Biology, Medicine (Hematology and Experimental Medicine), Microbiology & Immunology, Oncology (Clinical Research, Basic Cancer Research, Pharmacokinetics), Pathology, Pediatrics and Pharmacology & Therapeutics. It has now become a multi-institutional organization that reaches throughout McGill and beyond, including basic scientists and clinician scientists from 5 universities and 10 hospital-based or independent research institutes throughout Quebec. In 2000, the MCTRC was repositioned as the Montreal Centre for Experimental Therapeutics in Cancer (MCETC) in the context of an application to the Canada Foundation for Innovation (CFI).
That same year, the MCETC linked with the Centre de recherche clinique et evaluative en oncologie (CRCEO), based at the Centre de recherche of Hôtel Dieu du Quebec, to form the Axe Thérapeutique du Réseau de la Recherche sur le Cancer du FRSQ.
The Molecular Oncology research team includes internationally recognized researchers with expertise in the regulation of oncogene expression, signal transduction, evaluation of normal and malignant development in animal models, structural biology and bioinformatics. Their focus is on the molecular mechanisms underlying oncogenic development.
Role of MAF and CNC transcription factors in mammalian gene regulation, oncogenesis and differentiation.
Regulation of gene expression and signaling in cancer and immunity. Development of vaccines against cancer and viral diseases.
Molecular mechanisms of cancer development and treatment by regulation of protein synthesis and transcription factor Stat1.
Wilson H. Miller Jr.
Molecular mechanism of response and resistance of cancer cells to novel therapeutics.
Targeting Breast Tumour Kinase (BRK) in breast cancer therapy and validation of new targets for cancer, multiple sclerosis and obesity.
Understanding the mechanism by which tumour cell-derived ShcA signaling facilitate communication with the local microenvironment to promote the establishment of a pro-tumourigenic reactive stroma. To achieve this, Dr. Ursini-Siegel utilizes a genetic approach to alter ShcA signalling or expression in well characterized transgenic breast cancer mouse models.
Cancer Prevention and Cancer Genetics
The Cancer Prevention and Cancer Genetics group studies novel cancer therapies and cancer prevention strategies. Group members are involved in epidemiological, laboratory and clinical studies to examine the factors that contribute to the development and progression of tumours.
Hereditary cancer syndromes.
The roles of peptide growth factors, particularly insulin-like growth factors (IGFs), in the pathophysiology of neoplasia.
Characterizing the role of the Fanconi Anemia and other DNA repair genes in carcinogenesis, with particular emphasis on breast cancer.
Biomarkers in Cancer Therapy
Researchers involved in the biomarker discovery group are using recently discovered technologies which enable the screening of thousands of genes (genomics) or proteins (proteomics) on a single platform to identify biological markers that may serve to classify patients into higher or lower risk groups, or to serve as targets for “patient-tailored” therapy. Biomarkers can be identified from the tumour tissue itself or from blood. One advantage of studying blood biomarkers is that there is easy accessibility: samples can be obtained from patients via a simple blood test.
Investigating gene expression and DNA changes in breast and colon cancers.
Walter H. Gotlieb
Insulin-Like Growth Factor Receptor I targeting in epithelial ovarian cancer.
Micro-genetic analysis of cancer tissues.
Eph/Ephrin receptors and ligands in intercellular communication, cell death and cancer.
Genomic signature in melanoma progression and prognosis.
Androgen Receptor – Mechanism of action, genetic instability of androgen independent prostate carcinoma.
New Cancer Therapies: Development of Biological and Chemical Agents
Many of the Segal Cancer Centre’s researchers are looking at different chemical and biological approaches to the discovery and development of cancer therapies. Chemical agents refer to synthetic molecules, small peptides or natural products, whereas biological therapies use the patient’s immune system, either directly or indirectly, to fight cancer or to lessen the side effects that may be caused by some cancer treatments. This team exploits genomic and proteomic technologies, and bioinformatics to develop “smart” drugs against key targets for therapeutic intervention. It also focuses on understanding and tackling cancer drug resistance mechanisms that are often seen with chemotherapeutic agents. Members of this team include experts in cancer biology, cancer pharmacology, organic chemistry, molecular modeling and radiochemistry.
Understanding and targeting cellular signaling pathways regulating cancer cell invasion, in preclinical and clinical settings.
Disruption of DNA repair complexes in human cancer cells: Therapeutic implications.
Environmental carcinogens; Preclinical studies.
Development of gene therapy for the treatment of cancer; Regenerative medicine; Transgenic cell therapy.
Mechanisms of muscle wasting; Muscle metabolism; Cancer cachexia.
Development of novel arsenical-containing chemotherapies; Combination therapies; Environmental metal toxicology.
Restatement of cancer pharmacology: Improving anticancer drugs.
H. Uri Saragovi
Receptor-ligand interactions; Protein mimicry; Rational drug design; Receptor pharmacology.
Jian Hui Wu
Development of methods in computational biology & chemistry, and application of molecular modeling techniques to problems in chemistry and biology.
Radiopharmaceutical Chemistry/Radiobiology and Medical Physics
Radiation-induced normal tissue injury; VEGF; Isoprostanes; Radioprotectors; Optical Coherence Tomography.
Radiopharmaceutical chemistry; Neuroendocrine tumours.
Research Core Facilities
With the support of the CFI, the MCETC created state-of-the-art research platforms to accelerate research in cancer. These platforms include the following:
- Génome Québec/Lady Davis Institute Clinical Proteomics Facility
- Shirley and Max Konigsberg & Family Clinical Research Unit
- Flow Cytometry Unit
- High Performance Computing Facility
- Peptide Synthesis Laboratory
- George and Olga Minarik Research Pathology Facility
- Weekend to End Breast Cancer Cell Imaging Facility
- Jewish General Hospital Cell Preparation Centre