Transgenic Drosophila As A Drugscreening Tool In Multiple Cancers

Introduction: The selection of appropriate anticancer drugs in patients is a great challenge in cancer treatment. As medicine seeks to understand the difference between the “average” tumor and a tumor in an individual patient, there is great uncertainty regarding the effect of particular genes and drugs that target them. Transgenic Drosophila melanogaster has been proposed as a rapid and efficient system in which to generate a reliable model of an individual tumor and phenotypic screen for effective drugs. Such screens can potentially lead to the identification of a molecule that modifies a cancer phenotype by acting on a previously undescribed target or by acting simultaneously on more than one target.Methods: 97 Patients were assessed for genomic and clinical data. 12 patients had tumor genetics analyzed and models created that comprised driver mutations. 3 models were attempted in Drosophila and tested against 19 anticancer drugs.Results: 1 of 3 models was technically successful and advanced to drug screening. 5 drugs (gemcitabine, trametinib, crizotinib, doxorubicin, docetaxel) were predicted by the model to be effective against that particular cancer. However, neither of the two drugs used in the corresponding patient were predicted to be successful.Conclusions: While this project was unable to concretely validate the Drosophila modeling approach by accurately predicting treatment outcomes. I was able to develop and advance methods to predict the effects of a gene within a tumor and to develop one complete Drosophila model that responded to anticancer drugs in a dose-dependent manner. Further research is needed to assess the predictive value of these models.

This volume provides a series of review articles that capture the advances in using the fruit fly, Drosophila melanogaster, model system to address a wide range of cancer-related topics. Articles in this book provide case studies that shed light on the intricate cellular and molecular mechanisms underlying tumor formation and progression. Readers will discover the beauty of the fly model’s genetic simplicity and the vast arsenal of powerful genetic tools enabling its efficient and adaptable use. This model organism has provided a unique opportunity to address questions regarding cancer initiation and development that would be extremely challenging in other model systems. This book provides a useful resource for a researcher who wishes to learn about and apply the Drosophila model to tackle fundamental questions in cancer biology, and to find new ways to fight against this devastating disease.

Scientific Frontiers in Developmental Toxicology and Risk Assessment reviews advances made during the last 10-15 years in fields such as developmental biology, molecular biology, and genetics. It describes a novel approach for how these advances might be used in combination with existing methodologies to further the understanding of mechanisms of developmental toxicity, to improve the assessment of chemicals for their ability to cause developmental toxicity, and to improve risk assessment for developmental defects. For example, based on the recent advances, even the smallest, simplest laboratory animals such as the fruit fly, roundworm, and zebrafish might be able to serve as developmental toxicological models for human biological systems. Use of such organisms might allow for rapid and inexpensive testing of large numbers of chemicals for their potential to cause developmental toxicity; presently, there are little or no developmental toxicity data available for the majority of natural and manufactured chemicals in use. This new approach to developmental toxicology and risk assessment will require simultaneous research on several fronts by experts from multiple scientific disciplines, including developmental toxicologists, developmental biologists, geneticists, epidemiologists, and biostatisticians.

Nutrition has long been considered more the domain of medicine and agriculture than of the biological sciences, yet it touches and shapes all aspects of the natural world. The need for nutrients determines whether wild animals thrive, how populations evolve and decline, and how ecological communities are structured. 'The Nature of Nutrition' addresses nutrition's enormously complex role in biology, both at the level of individual organisms and in their broader ecological interactions.

Dedicated to the memory of George Lefevre in recognition of his exhaustive cytogenetic analysis of the X chromosome, The Genome of Drosophila melanogaster is the complete compendium of what is known about the genes and chromosomes of this widely used model organism. The volume is an up-to-date revision of Lindsley and Grell's 1968 work, Genetic Variations of Drosophila melanogaster. The new edition contains complete descriptions of normal and mutant genes including phenotypic, cytological, molecular, and bibliographic information. In addition, it describes thousands of recorded chromosome rearrangements used in research on Drosophila. This handbook and its accompanying polytene chromosome maps, are sturdily bound into the book as foldouts and available as a separate set, are essential research tools for the Drosophila community. Describes phenotype, cytology, and molecular biology of all recorded genes of Drosophila melanogaster, plus references to the literature Describes normal chromosome complement, special chromosome constructs, transposable elements, departures from diploidy, satellite sequences, and nonchromosomal inheritance Describes all recorded chromosome rearrangements of Drosophila melanogaster as of the end of 1989 Contains the cytogenetic map of all genes as of mid-1991 Contains the original polytene maps of C.B. Bridges, plus G. Lefevre's photographic equivalents, and the detailed maps of the chromosome arms produced by C.B. and P.M. Bridges All maps are reprinted as high-quality foldouts sturdily bound into the volume Maps may also be purchased separately in an eight-map packet, for laboratory and student use

The growing knowledge about disturbances of epigenetic gene regulation in hematopoietic stem cell disorders is now being translated into treatment approaches that target the epigenetic defects pharmacologically. This book first presents the latest evidence regarding the epigenetic regulation of hematopoietic stem cell differentiation and hemoglobin production. The significance of DNA methylation abnormalities in hematopoietic disorders and of epigenetic disturbances in lung cancer and other solid tumors is then discussed. A major part of the book, however, relates specifically to the translation of basic research and drug development to clinical applications, and in this context both present and future clinical strategies are considered. Individual chapters are devoted to the use of DNA hypomethylating agents and chromatin-modifying agents, and the treatment of hematologic malignancies and solid tumors by means of epigenetic agents is discussed in detail.

A link between inflammation and cancer was initially made by Rudolf Virchow back in the 19th century. Nowadays many cancers are considered dependent on inflammatory responses to microbial and damaged-self stimuli and both arms of immunity, innate and adaptive, are playing a role in promoting cancer. Moreover, besides environmental factors, opportunistic pathogens contribute to inflammation and cancer. Nevertheless, microbial influence on chronic disease is sometimes difficult to discern, especially in the context of polymicrobial communities, such as those found in the digestive tract. In this light, model organisms provide important insights into immune and growth signals that promote cancer, and suggest therapies that will selectively target potentially harmful microbes or modulate host responses. A number of review and opinion articles in this series address novel aspects and paradigms of the interactions between the microbiota and the host in relation to inflammation and cancer.

A second edition of the classic handbook has become a standard in the Drosophila field. This edition is expanded to include topics in which classical genetic strategies have been augmented with new molecular tools. Included are such new techniques as homologous recombination, RNAi, new mapping techniques, and new mosaic marking techniques.

Topic Editor Prof. Aimin Xu receives financial support from Servier Laboratories. The other Topic Editors declare no competing interests with regards to the Research Topic theme.