News Article | September 8, 2016
When 28 distinguished individuals convened earlier this year to help shape the scientific mission at the National Cancer Institute (NCI) of Vice President Joe Biden's National Cancer Moonshot Initiative, they were given five months to draft guidelines to accelerate cancer research, prevention and care. On Wednesday, the National Cancer Advisory Board approved the Blue Ribbon Panel's 10 recommendations. "In a very limited amount of time we were able to come together to address important topics to help Vice President Biden's mission to make a decade's worth of advances in cancer prevention, diagnosis and treatment in just five years," said Blue Ribbon Panel member, María Elena Martínez, PhD, Sam M. Walton Endowed Chair for Cancer Research at University of California San Diego School of Medicine and co-lead of the Moores Cancer Center's Reducing Cancer Disparities research program. "My hope is that not just the National Cancer Institute, but other organizations and industry as well, take these recommendations to heart and contribute to moving these guidelines forward." Martínez co-chaired the Implementation Science Working Group, which was tasked with drafting recommendations that improve cancer outcomes by identifying and testing methods that more effectively implement evidence-based interventions for cancer prevention, risk assessment, screening and early detection, and prognosis, treatment and survivorship. "In some areas of cancer research, be it prevention or treatment, we actually have evidence of what works," said Martínez. "A lot of research goes behind these guidelines. In some populations, specifically those that do not have the means to get to a physician, to get to a hospital, who don't have health insurance, these guidelines don't get implemented. Some of it has to do with educating the community, making sure they are part of the implementation of these guidelines and that they're at the forefront of moving this forward." The group recommended expanding use of proven prevention and early detection strategies to further address tobacco cessation, colorectal cancer screening, vaccination for the human papillomavirus (HPV) and screening for hereditary cancer syndromes. This recommendation has the potential to impact large populations through prevention strategies. In the United States, only 50 to 60 percent of people are screened for colorectal cancer; the figure drops to 20 to 30 percent among low-income individuals, said Martínez. HPV vaccinations rates are worse, with only 40 percent of age-eligible girls and 20 percent of age-eligible boys completing the recommended vaccine dosage. "The bold but feasible cross-cutting initiatives in this report will improve outcomes for patients with cancer, prevent cancer and increase our understanding of cancer," said Douglas Lowy, MD, NCI acting director. "NCI stands ready to accelerate cancer research in the critical areas identified by the Blue Ribbon Panel."
Many biomedical researchers are striving to make sense of the flood of data that has followed recent advances in genomic sequencing technologies. In particular, researchers are often limited by the challenge of getting multiple bioinformatics tools to "talk" to one another. To help address this need, researchers at University of California, San Diego School of Medicine, in collaboration with labs at the Broad Institute of MIT and Harvard, Stanford University, Weizmann Institute and Pennsylvania State University, developed GenomeSpace, a cloud-based, biologist-friendly platform that connects more than 20 bioinformatics software packages and resources for genomic data analysis. The team is now developing and crowdsourcing "recipes"—step-by-step workflows—to better enable non-programming researchers to interpret their genomic data. The work is described in a paper published January 18, 2016 in Nature Methods. "Now that new sequencing technologies can produce significantly greater amounts of data than they could a decade ago, the methods required to analyze that data must be correspondingly more powerful," said Jill Mesirov, PhD, associate vice chancellor for computational health sciences and professor of medicine at UC San Diego School of Medicine and Moores Cancer Center. "The problem is that only a small portion of the biomedical research community has the expertise to know the right method, or combination of methods, to solve their research questions and the best way to apply those methods to their data." Before GenomeSpace, it was extraordinarily difficult for researchers, especially without programming skills, to get many of the available analysis tools to work together. Users needed to know how to write short computer programs in order to transform and transfer data between platforms. GenomeSpace now performs this service seamlessly with a user-friendly interface, connecting popular genomic data analysis tools such as Cytoscape, Galaxy, GenePattern and the Integrative Genomics Viewer (IGV). Several of these tools are themselves "tool aggregators," so in linking them, GenomeSpace provides access to hundreds of bioinformatics analyses. What's more, GenomeSpace doesn't just leave users on their own to determine the best tools for their particular research questions. The site also provides "recipes"—easy-to-follow example workflows that clearly demonstrate the sequence of tools researchers should use to get the information they are looking to extract from their raw data. GenomeSpace currently provides 13 recipes. The platform's developers are now inviting the user community to contribute their own additional recipes. "No individual lab can possibly develop all the right useful recipes—crowdsourcing will help make GenomeSpace even more useful to non-programming researchers," said Michael Reich at UC San Diego School of Medicine, who leads the GenomeSpace development team. Here's how an example GenomeSpace recipe works: A researcher wonders if there is a specific set of genes that leukemia stem cells express differently than normal white blood cell precursors. She also wants to better understand the biological mechanism underlying those differentially expressed genes but doesn't know where to start. With GenomeSpace, the researcher can simply upload the gene expression data and other information about the two cell types (the "ingredients") and follow a GenomeSpace recipe, designed specifically for these types of research questions. In this case, the recipe tells the researcher how to run the data ingredients through two tools available in GenomeSpace: 1) GenePattern, which finds a list of the 50 genes that differ the most between the two cell types and 2) Cytoscape, which identifies how proteins associated with these genes interact in networks, thus providing clues to the roles that tumor-specific or normal cell-specific genes play in the body. This type of information provided by GenomeSpace could help the researcher better understand how leukemia develops and help identify possible targets for new therapeutics, said Reich. "Our recipe resource was modeled on Tom Maniatis' classic, Molecular Cloning: A Laboratory Manual. We hope, with a combination of our own development and crowdsourcing, to grow the resource and increase its breadth," Mesirov said. "It's our long-term goal to convert these descriptive workflows into more dynamic, interactive interfaces making them even easier to follow." — Kun Qu et al. Integrative genomic analysis by interoperation of bioinformatics tools in GenomeSpace, Nature Methods (2016). DOI: 10.1038/nmeth.3732
Font-Burgada J.,Moores Cancer Center |
Sun B.,Nanjing Medical University |
Karin M.,Moores Cancer Center
Cell Metabolism | Year: 2016
Although discussion of the obesity epidemic had become a cocktail party cliché, its impact on public health cannot be dismissed. In the past decade, cancer had joined the list of chronic debilitating diseases whose risk is substantially increased by hypernutrition. Here we discuss recent advances in understanding how obesity increases cancer risk and propose a unifying hypothesis according to which the major tumor-promoting mechanism triggered by hypernutrition is the indolent inflammation that takes place at particular organ sites, including liver, pancreas, and gastrointestinal tract. The mechanisms by which excessive fat deposition feeds this tumor-promoting inflammatory flame are diverse and tissue specific. © 2016 Elsevier Inc.
Cloughesy T.F.,University of California at Los Angeles |
Cavenee W.K.,Ludwig Institute for Cancer Research |
Cavenee W.K.,Moores Cancer Center |
Mischel P.S.,Ludwig Institute for Cancer Research |
And 2 more authors.
Annual Review of Pathology: Mechanisms of Disease | Year: 2014
Glioblastoma (GBM) is one of the most lethal human cancers. Genomic analyses are defining the molecular architecture of GBM, uncovering relevant subsets of patients whose disease may require different treatments. Many pharmacological targets have been revealed, promising to transform patient care through targeted therapies. However, for most patients, clinical responses to targeted inhibitors are either not apparent or not durable. In this review, we address the challenge of developing more effective, molecularly guided approaches for the treatment of GBM patients. We summarize the current state of knowledge regarding molecular classifiers and examine their benefit for stratifying patients for treatment. We survey the molecular landscape of the disease, discussing the challenges raised by acquired drug resistance. Furthermore, we analyze the biochemical features of GBM, suggesting a next generation of drug targets, and we examine the contribution of tumor heterogeneity and its implications. We conclude with an analysis of the experimental approaches and their potential benefit to patients. © 2014 by Annual Reviews. All rights reserved.
Piccioni D.E.,Moores Cancer Center |
Kesari S.,Moores Cancer Center
Expert Review of Anticancer Therapy | Year: 2013
Despite recent scientific advances in the understanding of the biology of malignant gliomas, there has been little change in the overall survival for this devastating disease. New and innovative treatments are under constant investigation. Starting in the 1990s, there was an interest in using viral therapeutics for the treatment of malignant gliomas. Multiple strategies were pursued, including oncolytic viral therapy, enzyme/pro-drug combinations and gene transfer with viral vectors. Multiple Phase I and II trials demonstrated the safety of these techniques, but clinically showed limited efficacy. However, this led to a better understanding of the pitfalls of viral therapy and encouraged the development of new approaches and improved delivery methods. Here we review the prior and ongoing clinical trials of viral therapy for gliomas, and discuss how novel strategies are currently being utilized in clinical trials. © 2013 Informa UK Ltd.