International research collaboration can successfully address the global health program of cancer through access to unique populations and environments, shared resources, specialized expertise, new concepts and perspectives, innovative methodologies and/or emerging technologies. However, barriers to sustaining these collaborations exist such as the lack of funding and the sharing of knowledge about these important research partnerships. This grant provides support for highly meritorious research that is being conducted collaboratively by investigators in different countries around the world. The goals of the award are to: promote international cancer research collaboration as an effective means to accelerate progress against cancer; provide the support necessary to sustain and enhance highly meritorious international cancer research collaborations; foster interactions between and among cancer scientists and disseminate the scientific knowledge gained from international collaboration; and contribute to a global impact against cancer.
2011 GRANTEE
Timothy R. Rebbeck, Ph.D.Professor, University of Pennsylvania School of Medicine, Philadelphia, PA
African Centers of Excellence in Prostate Cancer Research
Prostate cancer is one of the most common cancers in Africa and in men of African descent worldwide. IARC predicts that prostate cancer deaths in Africa will more than double from 28,006 in 2008 to 57,048 by 2030. While the majority of prostate cancer cases in the U.S. are diagnosed at an early (treatable) stage, the majority of African prostate cancer cases are and will likely continue to be diagnosed at late (usually untreatable) stages. Therefore, prostate cancer represents a significant and under-studied public health problem in Africa.
The African Centers of Excellence (ACE) bring together investigators interested in studies of prostate cancer in Africa and develop multicenter collaborative research. The overarching aim of this research is to understand prostate cancer incidence, mortality, prevention and treatment of prostate cancer in men of African descent. While the ACE consortium will focus on Africa, the consortium will also include men of African descent in North America, Europe and the Caribbean.
The ACE consortium will focus on the following activities:
- Undertake descriptive and analytical epidemiology studies to understand the magnitude of the prostate cancer burden and identify relevant risk factors for prostate cancer etiology and outcomes;
- Undertake studies of inherited genotypes for prostate cancer etiology and outcomes, including studies that confirm known (e.g., GWAS-identified) loci as well as novel gene discovery in Africans;
- Undertake studies of somatic (tumor) biomarkers, including ETS fusion proteins, telomere length, infection (including XMRV and others), and miRNA, genomic expression studies, and other relevant biomarkers to better understand prostate cancer etiology and prognosis.
The ACE consortium will establish necessary research infrastructure to address an important and increasing cancer problem in Africa. The knowledge gained from studies of aggressive disease in Africa may in turn improve our understanding of aggressive prostate cancer diagnosed anywhere in the world.
2010 GRANTEE
Ralph H. Hruban, M.D.Professor of Pathology and Oncology, Johns Hopkins University, Baltimore, MD
Johns Hopkins- Garvin Institute Pancreatic Cancer Collaboration
Pancreatic cancer is the fourth leading cause of cancer death in the United States. It is estimated that this year 37,680 Americans will be diagnosed with pancreatic cancer, and that 34,290 will die from the disease. Pancreatic cancer has the worst one- and five-year survival rates of any cancer. The Johns Hopkins-Garvan Institute Pancreatic Cancer Alliance builds on a well-established collaboration between the pancreatic cancer research team at Johns Hopkins and scientists at the Garvan Institute in Australia. The investigators will use a novel genetically engineered mouse to foster the efficient and rapid creation of cell lines from surgically resected human pancreatic cancers. These cell lines will then be completely sequenced through the International Cancer Genome Consortium. The sequencing of these well-annotated pancreatic cancers can then be directly translated to patient care. The Johns Hopkins-Garvan Institute Pancreatic Cancer Alliance will use the information gleaned from sequencing to identify novel gene-specific targets that can form the basis for new ways to treat pancreatic cancer. They will also use the data generated to study why pancreatic cancer runs in some families, and to build gene-specific early detection tests. Simply put, the goal of this exciting alliance is to advance our understanding of the fundamental nature of pancreatic cancer.
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2009 GRANTEE
Josep M. Llovet, M.D.
Associate Professor of Medicine, Institut D'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
Oncogenic Addiction and Gatekeeper Genes in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) represents the third-leading cause of cancer-related deaths worldwide, but only one molecular therapy - sorafenib - is effective so far. In order to accelerate the knowledge of the pathogenesis of this cancer and the development of targeted therapies, we assembled an international multidisciplinary consortium of basic and translational researchers, the HCC Genomic Consortium, led by Dr. Josep M. Llovet and collaborators from Mount Sinai (New York), Dana-Farber-MIT (Boston), Hospital Clinic (Barcelona) and National Cancer Institute (Milan). As a result of the research conducted by the consortium, we recently identified VEGFA high-level amplifications in HCC, demonstrated that inhibition of mTOR signaling ameliorates tumor progression in experimental models and generated a gene signature from the adjacent tumoral tissue that predicts patient outcome after surgical resection. The 2009 Landon Foundation-AACR INNOVATOR Award for International Collaboration in Cancer Research will further support a novel project of the consortium aimed to assess novel mutations in oncogenes or tumor suppressor genes (TSG) that can provide markers of early detection and identify the driving molecular events that may represent targets for molecular therapies. For that purpose, we will survey the mutation status of 141 commonly mutated genes in a large cohort of preneoplastic nodules and human HCC samples and will integrate the molecular information (i.e. mutation data, gene expression dysregulation, signaling pathway activation and progenitor cell markers) with clinical outcome to define the potential drivers in each molecular subclass. This study might identify unknown gatekeeper genes and oncogenic addiction loops in HCC patients, which will lead toward better preventive and therapeutic strategies.
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2008 GRANTEE
Michele Carbone, M.D., Ph.D.
Director, Cancer Research Center of Hawaii and John A. Burns School of Medicine, Honolulu, HI
Gene Environment Interaction and Early Detection of Mesothelioma in Cappadocia, Turkey
"Malignant mesothelioma is the cancer of the membranes that surround the lungs and the abdomen. It is incurable unless detected in its earlier stages: current therapies have little or no effect and survival is one year from diagnosis. The incidence of mesothelioma has increased more than that of any other cancer in the past 50 years. This increase is related mostly to the use of asbestos in the shipping and construction industries. About 25 million Americans have been exposed to asbestos and are at risk of developing mesothelioma. In addition, erionite, a type of mineral fiber that shares some physical characteristics with crocidolite asbestos, and that is naturally present in the U.S. and in other countries causes mesothelioma. To develop effective strategies for early detection and prevention, we must identify among the many millions of exposed individuals those at higher risk. In three villages in Cappadocia, Turkey, there is a unique epidemic of mesothelioma: 50 percent of all deaths are caused by mesothelioma. We discovered that this epidemic occurs in some families but not in others and that when members of high-risk families marry into low-risk families mesothelioma occurs in the descendents. When high-risk family members are born and raised outside these three villages, mesothelioma does not occur. We discovered that this epidemic is caused by the interaction of erionite with genetics. We also found that mesothelioma is very frequent in some U.S. families. My hypothesis is that these families are very susceptible to mineral fiber carcinogenesis, and that erionite plays a major role in Turkey, while asbestos plays a role in the U.S. families. We have also discovered novel serological markers for early detection of mesothelioma. I have now organized an international team of scientists to: 1) identify the gene or genes that predispose certain families in the U.S. and in Turkey to mineral fiber (asbestos and erionite) carcinogenesis; and 2) to validate the specificity and sensitivity of the serological markers we discovered for early detection. The funding from the AACR Landon Foundation will be devoted to support these projects. The isolation of the mesothelioma gene will allow us to design specific preventive/therapeutic approaches for mesothelioma. The validation of the sensitivity and specificity of the serological markers for early detection in the high-risk population in Turkey will allow us to offer this screening to the workers at risk of developing mesothelioma because of asbestos exposure. By detecting mesothelioma in its early stage we should be able to cure these patients before the tumor invades other organs and becomes incurable. Therefore, the results of these studies will benefit many million people exposed to asbestos and to other carcinogenic mineral fibers in the U.S. and worldwide. "
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