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  • Promising advances in cancer therapy stemming from an increasing understanding of the molecular and genetic underpinnings of the tumorigenic process have been fueled by a strong, determined scientific community, influential patient advocacy groups and committed funding bodies. Despite these efforts, the development of effective drugs to prevent systemic dissemination of cancer cells or to eliminate overt metastasis in secondary organs remains a challenge to both researchers and physicians. In an attempt to tackle the most relevant and timely translational issues, a meeting held in 2012 as a result of a successful partnership between the Volkswagen Foundation and Nature Medicine brought together a group of metastasis research experts to identify the most important hurdles and help create a framework for potential clinical and translational strategies.

    • Thomas Brabletz
    • David Lyden
    • Zena Werb
  • Distinct roadblocks prevent translating basic findings in viral pathogenesis into therapies and implementing potential solutions in the clinic. An ongoing partnership between the Volkswagen Foundation and Nature Medicine resulted in an interactive meeting in 2012, as part of the “Herrenhausen Symposia” series. Current challenges for various fields of viral research were recognized and discussed with a goal in mind—to identify solutions and propose an agenda to address the translational barriers. Here, some of the researchers who participated at the meeting provide a concise outlook at the most pressing unmet research and clinical needs, identifying these key obstacles is a necessary step towards the prevention and cure of human viral diseases.

    • Steven Deeks
    • Christian Drosten
    • JoAnn Suzich
  • Pathogens have remarkable abilities to flout therapeutic intervention. This characteristic is driven by evolution, either as a direct response to intervention (for example, the evolution of antibiotic resistance) or through long-term co-evolution that generates host or parasite traits that interact with therapy in undesirable or unpredicted ways. To make progress towards successful control of infectious diseases, the concepts and techniques of evolutionary biology must be deeply integrated with traditional approaches to immunology and pathogen biology. An interdisciplinary approach can inform our strategies to control pathogens or even the treatment of infected patients, positioning us to meet the current and future challenges of controlling infectious diseases.

    • Tom J Little
    • Judith E Allen
    • Nick Colegrave
  • Animal models are indispensable for studying disease pathogenesis and discovering new treatments for human organ-specific autoimmune diseases. However, there is a need of more refined paradigms for these models. Ideally, a small-animal model should represent the clinical features of human disease in their entirety. Disease in the animals should develop spontaneously, should be followed over an extended period of time and should involve the genetic, molecular and cellular elements that contribute to human pathogenesis.

    • Hartmut Wekerle
    • Alexander Flügel
    • David Serreze
  • Recent progress has revealed the molecular basis of how self-reactive T cells are normally generated in the immune system and differentiate into autoimmune effector T cells and how they are controlled by central and peripheral mechanisms of self-tolerance. There is also evidence that target tissues and cells in autoimmune disease have different sensitivities to immune mediators. Here we describe how these basic findings can be clinically translated to re-establish self-tolerance in individuals with autoimmune disease.

    • Shimon Sakaguchi
    • Fiona Powrie
    • Richard M Ransohoff
  • Translational research in autoimmunity is hampered by a number of hurdles, including a lack of knowledge regarding initiating and pathologically relevant autoantigens, the low frequency of autoreactive pathogenic B and T cells, difficulty in accessing the affected tissue, differences between self-reactive and pathogen-specific lymphocytes, a lack of etiologically relevant preclinical animal models and the heterogeneity of disease presentation. Given the need for biomarkers and new therapeutics, it is imperative that these hurdles be surmounted.

    • Bart O Roep
    • Jane Buckner
    • Frauke Zipp
  • Autoimmune diseases have a complex etiology and despite great progress having been made in our comprehension of these disorders, there has been limited success in the development of approved medications based on these insights. Development of drugs and strategies for application in translational research and medicine are hampered by an inadequate molecular definition of the human autoimmune phenotype and the organizational models that are necessary to clarify this definition.

    • Richard S Blumberg
    • Bonnie Dittel
    • Frank O Nestle
  • Great strides have been made in our understanding of the pathogenesis of autoimmune diseases. Research has identified genetic associations, new functional subsets of effector and regulatory T cells and the gut microbiota as crucial environmental factors in regulating immune function. This commentary discusses recent advances in our understanding of genetic and environmental factors as well as the role of innate and adaptive immune responses in driving immune-mediated tissue injury.

    • Vijay K Kuchroo
    • Pamela S Ohashi
    • Carola G Vinuesa
  • There are multiple immune-based therapeutics available for some of the most prevalent autoimmune diseases, but for others, there are few or no approved immune therapies. This dichotomy poses discrete challenges. First, for diseases in which multiple therapy choices exist, a rational decision tree is required to select the best therapy. Second, we must devise new strategies for the autoimmune diseases that have the highest unmet clinical need. This commentary outlines new strategies for designing more efficient and selective approaches for immune therapy of autoimmune diseases.

    • Lawrence Steinman
    • Joan T Merrill
    • Mark Peakman
  • Although the pathological hallmarks of neurodegenerative diseases have been described for over 100 years, our understanding of the molecular events leading to neuronal death has emerged over the past two decades. Despite all of this progress in basic research, why do we still lack disease-modifying therapeutics?