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.
David P. Carbone, M.D., Ph.D.
Professor of Med., Cancer Biology Hem./Onc., Ohio State University, Columbus, OH
Molecular profile of lung adenocarcinoma in Brazil
The current project is intended to establish, in a comprehensive manner, the molecular profile of lung adenocarcinoma in Brazil. Centers from the five geographic regions in Brazil will be working together to enroll patients and collect clinical and epidemiological data, which will enable comparative analyses between them. This study is pivotal in the sense that a prospective cohort will be included, which tends to minimize eventual selection bias and generate a more updated evaluation. Moreover, the molecular tests will be conducted in a single institution, using a modern Next Generation Sequencing platform. This technology allows numerous genes to be evaluated in the same experiment, with a single sample of DNA. It should be an important advantage in lung cancer, since small tumor specimens are routine in lung biopsies. Furthermore, a high sensitivity is achieved due to repetitive coverage of each gene assessed. This study will give support to the Brazilian National Policies in Cancer Control, and hopefully support the incorporation of established targeted therapies in the Brazilian public health care program (Sistema Único de Saúde – SUS).
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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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