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A Broad-Spectrum Integrative Design for Cancer Prevention and Therapy

This Halifax Project1 task force focused on "A Broad-Spectrum Integrative Design for Cancer Prevention and Therapy".  180 participating scientists from 22 countries were formed into 12 teams (see below) because the current approach to cancer chemotherapy (i.e., one that focuses mainly on cytotoxics and/or chemicals aimed at single targets) has serious limitations that must be improved upon. While some important therapeutic gains have certainly been achieved using the current biomarker-driven, personalized approach to therapy, disease relapse (caused by intra-tumoral heterogeneity and adaptive resistance) continues to be a significant ongoing problem in the clinic. At the same time, drug toxicities and multiple drug resistance issues have severely constrained the physician’s ability to pursue more than just a handful of relevant targets in refractory cancers. Consequently, this task force leveraged the rapid advances in our knowledge of the mechanics of the disease to develop a robust and non-toxic, broad-spectrum approach to both prophylaxis and therapy (i.e., one that will be aimed at many prioritized targets simultaneously). In essence, this group has the foundation for a ground-breaking new direction in translational research that will be able to address the many mutations that make this disease so difficult to stop.  This work was captured in a special issue of Elsevier’s Seminars in Cancer Biology (2014 Impact Factor: 9.330)  - click here for details.  The capstone paper from this effort can be found here.

The teams that worked on this project are shown below.

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Lasse Dahl Jensen, PhD, Karolinska Institutet And Linkoping University (Sweden) - Dr. Jensen is the scientific head of the zebrafish facility at Linkopings University, a position that he has filled since 2011. He is also associated as a junior group leader in Prof. Yihai Cao's lab at the Karolinska Institute. Dr. Jensen received a civil engineering degree (masters in biotechnology) from the Technical University of Denmark and did his Ph.D at the Karolinska Insititute. Since then Dr. Jensen has completed two short post docs at the Karolinska Institute and Linkoping University. Dr. Jensen has for 8 years contributed to the field of tumor angiogenesis, as well as angiogenesis in general using mainly zebrafish and mouse models as his experimental platform. Currently he is focused on hypoxia and circadian signaling pathways and how they regulate physiological and pathological angiogenesis, including tumor angiogenesis.
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Deregulated metabolism
Matthew Hirschey, PhD, Duke University (United States) - Assistant Professor in the Department of Medicine, Division of Endocrinology, Metabolism and Nutrition and in the Department of Pharmacology & Cancer Biology at Duke University Medical Center, and faculty member of the Sarah W. Stedman Nutrition and Metabolism Center at Duke. Dr Hirschey's research focuses on genes, proteins, and pathways that control metabolism, and his lab explores different aspects of the biology of mitochondrial energy production as a crucial cellular process which is an important regulator of human health and diseases such as cancer.
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Evasion of Anti-growth Signalling
Dong M. Shin, MD, FACP, Emory University (United States) - Professor of Hematology and Oncology, and Otolaryngology; Associate Director of Academic Development for Emory Winship Cancer Institute and Director of the Emory Winship Cancer Chemoprevention Program. Dr. Shin's research focus is in head, neck and lung cancers. During the past 20 his research has been in the following areas: Establishing carcinogenesis models in preclinical and clinical settings for head, neck and lung cancer; developing biomarkers in animal and human carcinogenesis for head, neck and lung cancer; developing molecular targeted prevention and therapies using epidermal growth factor receptor (EGFR) signaling pathways (i.e., EGFR monoclonal antibodies, EGFR tyrosine kinase inhibitors cyclooxygenase-2 (COX-2) inhibitors and other molecular targeted molecules including green tea polyphenons; and developing novel therapeutics (clinical or translational protocols) for head and neck cancer, lung cancer, thymoma and mesothelioma. He is also currently focused on new drug delivery to cancer patients using nanotechnology.
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Genetic Instability
Lynnette Ferguson, DPhil, DSc, The University Of Auckland (New Zealand) - Professor at the Auckland Cancer Society Research Centre and the Head of the Department Nutrition Department in the School of Medical Sciences at The University of Auckland in New Zealand. Dr Ferguson's current research considers the interplay between genes and diet in the development of chronic disease, with particular focus on inflammatory bowel disease and prostate cancer
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Immune System Evasion
Byoung S. Kwon, PhD, National Cancer Center (Korea South) - Endowed Investigator in the Division of Cell and Immunobiology, R&D Center for Cancer Therapeutics, National Cancer Center Goyang , Republic of Korea and Professor of the Department of Medicine at Tulane University, in New Orleans, LA, USA. Dr Kwon's research interests include communication network of immune cells and he has published extensively on immunotherapy against cancers and autoimmune diseases.
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Replicative Immortality
Paul Yaswen, PhD, Life Sciences Division, Lawrence Berkeley National Lab (United States) - Dr Yaswen's lab studies pathways that govern proliferative potential in human epithelial stem and progenitor cells. While the p16INK4A gene is best known for its role in tumor suppression, it also plays a role in stem cell commitment. His group has shown that the repressive effect of p16 on hTERT (encoding the catalytic subunit of telomerase), can be dissociated from the repressive effect of p16 on genes required for cell cycle progression, raising the possibility that a heirarchy of p16 functions exist, and that p16-associated senescence is an aberrant differentiation response to internal or external stresses. Telomerase expression is critical for the unlimited proliferative potential of human stem cells, but is repressed in most other lineage restricted and differentiated somatic cells, probably as a mechanism for tumor suppression. His group studies the regulation of telomerase expression in human epithelial cells cultured in physiologically relevant microenvironments.
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Resistance to Apoptosis
Ramzi Mohammad, Ph.D., Karmanos Cancer Institute Wayne State University (United States) - Professor, Department of Oncology and Director of GI Research. Dr. Mohammad's research is translational and through close work with clinicians he has introduced several experimental drugs into the clinic including Bryostatin-1, Aurastatin-PE, Dolastatin-10 and cambertastatin-4 and small molecule inhibitors of Bcl-2 such as AT-101 (gossypol) and HMD2. His lab has new BH3-mimetic small molecule inhibitor that disarms anti-apoptotic Bcl2-family proteins. They have also established mouse xenograft models from pancreatic cancer, colon cancer and lymphoma and leukemia, facilitating studies of drug efficacy and mechanism of action in vivo. Currently, his lab is investigating several SMIs including novel HDM2 inhibitors and Mcl-1 inhibitors. Dr. Mohammad has more than 25 years of cancer research experience, with extensive experience in molecular biology, animal models and tissue culture. He has established a number of pancreatic cancer and other hematological malignancies cell lines and was among the first to establish pancreatic orthotopic models.
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Sustained Proliferative Signalling
Mark Feitelson, PhD, Temple University (United States) - Professor in the Department of Biology and Co-Director of the Temple University Biotechnology Center at Temple since 2007, Dr Feitelson focuses his research on the hepatitis B and C viruses and their role in engendering liver cancer. The hepatitis B virus (HBV) is among the most common infections in the world, affecting approximately 2 billion people (mostly in developing countries in Asia and Africa). In effect, the hepatitis B and C viruses cause their host cells to acquire the quick growth and resistance to immune elimination characteristics of cancer cells in the course of promoting their own survival. Liver cancer itself often follows. The current model for managing aggressively mutating viral infections is combination therapies, or "drug cocktails." Feitelson has formed strong ties with the HBV research community in China where HBV-associated diseases are a national priority.
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Tissue Invasion and Metastasis
Wen G. Jiang, MD, PhD, Cardiff University School Of Medicine (United Kingdom) - Professor of surgery and tumour biology at the Cardiff University School of Medicine, Cardiff, UK. Dr. Jiang leads a team with an interest in cancer. Professor Jiang graduated from the Beijing Medical University (presently Peking University Health Science Centre) in 1984 and had worked in Peking's First Teaching Hospital (BeiDa Hospital) as a Surgical Resident and Chief Surgical Resident. He came to Cardiff in 1989 and studied his M.D. degree at the University of Wales College of Medicine (currently Cardiff University School of Medicine) and received his M.D. degree in 1995. He was a Senior Lecturer and Reader at the Cardiff University and was appointed to the current Chair position in 2004. Professor Jiang's main academic interest is cancer metastasis and angiogenesis in solid tumours including breast and prostate cancer.
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Tumor Microenvironment
Dean Felsher, MD, PhD, Stanford University (United States) - Professor of Medicine and of Pathology at Stanford School of Medicine, Stanford University, California, USA. Dr Felsher's research interests include both basic science and translational research studies that investigate how oncogenes initiate and sustain tumorigenesis. He is a 1996 Lymphatic Research Foundation Fellow and 2001 Junior Faculty Award Recipient. His laboratory has developed model systems that can conditionally activate oncogenes in normal human and mouse cells in tissue culture or in specific tissues of transgenic mice.
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Tumor Promoting Inflammation
Anupam Bishayee, PhD, American University Of Health Sciences School Of Pharmacy (United States) - Founding Chair and Professor in the Department of Pharmaceutical and Administrative Sciences in the School of Pharmacy, American University of Health Sciences, Signal Hill, California. Dr Bishayee's research for the last 17 years focuses on elucidation of the protective, chemopreventive and therapeutic effects of medicinal plants and natural products and their synthetic analogs in pre-clinical animal models of breast, prostate and liver cancer. His current research program aims to investigate mechanism-based chemopreventive and therapeutic modalities of dietary and plant-based phytochemicals, including resveratrol from grapes, anthocyanans from berries as well as ellagitinins from pomegranates, in pre-clinical models of breast and liver cancer.
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Validation Team
Kanya Honoki, MD, PhD, Nara Medical Univeristy (Japan) - Assistant professor and chief of musculoskeletal oncology unit in the Department of Orthopedic Surgery, Arthroplasty and Regenerative Medicine at Nara Medical University, Japan. Expertized in basic and clinical orthopedic oncology, cancer cell biology and stem cell biology, regenerative and restorative medicine. Has been working mainly on the pathogenesis of sarcomas using own-established rat sarcoma model and human materials, focusing on molecular and cellular mechanisms of disease progression such as invasion, metastasis and drug-resistance, which includes a role of stem cell population in sarcomas. Current research interest is stem cell aging and cancer development. Engaged as an active member of both American and European Association for Cancer Research, Japanese Cancer Association and International Society for Stem Cell Research, and also an editorial board member and reviewer of several international societies and journals including European Science Foundation, PLosOne, British Journal of Cancer, Cancer Chemotherapy and Pharmacology, Cell Biology International.
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