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.
Judith A. Varner, Ph.D.
Professor of Medicine, Moores Cancer Center, University of California San Diego, La Jolla, CA
Targeting Tumor Inflammation: A New Approach to Treat Pancreatic Cancer
"An increasing body of knowledge indicates that chronic inflammation promotes tumor development and progression. Tumor-associated macrophages comprise up to 25 percent of the mass of tumors but little of normal tissues; these cells promote immunosuppression, angiogenesis, fibrosis and resistance to chemotherapy, thereby stimulating tumor growth and metastasis. Targeting inflammation could provide substantial therapeutic benefit in pancreatic ductal adenoma carcinoma and other cancers for which there is no effective therapy.
"The objective of this international collaboration between the Judith Varner laboratory at the University of California, San Diego, in the United States and the Hirsch laboratory at the University of Torino in Italy is to identify molecular mechanisms regulating pancreatic tumor inflammation and its contribution to pancreatic tumor growth and metastasis. During the course of our ongoing collaboration, we found that macrophage phosphatidyl inositol (3,4,5) kinase gamma isoform (PI3K?amma) plays a central role in promoting tumor inflammation by mediating recruitment of pro-angiogenic, immunosuppressive myeloid cells to tumors, including melanoma, lung, breast and pancreatic tumors. Inhibition of PI3K?amma blocked tumor inflammation, immunosuppression and angiogenesis, thereby suppressing tumor growth and metastasis. These studies indicate that selectively targeting tumor inflammation could provide significant benefit in the treatment of pancreatic ductal carcinoma (PDAC).
"The Landon Foundation-AACR INNOVATOR Award for International Collaboration in Cancer Research will promote and extend these studies by enabling us to evaluate the capacity of PI3K? inhibition to ameliorate pancreatic cancer in mouse models of PDAC. We will also determine whether PI3K?amma inhibitors can enhance the efficacy of anti-tumor vaccines. These studies will determine whether therapeutic inhibition of PI3K?amma can suppress pancreatic tumor growth and metastasis."
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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."