Cancer is a multistep disease driven by the activation of specific oncogenic pathways concomitantly with the loss of function of tumor suppressor genes that act as sentinels to control physiological growth. The conservation of most of these signaling pathways in Drosophila , and the ability to easily manipulate them genetically, has made the fruit fly a useful model organism to study cancer biology. In this review we outline the basic mechanisms and signaling pathways conserved between humans and flies responsible of inducing uncontrolled growth and cancer development. Second, we describe classic and novel Drosophila models used to study different cancers, with the objective to discuss their strengths and limitations on their use to identify signals driving growth cell autonomously and within organs, drug discovery and for therapeutic approaches.

Epidemiological and preclinical studies have demonstrated that bioactive foods like flavonoids, polyphenolic compounds derived from fruits and vegetables, exert a protective action against obesity, cardiovascular disorders, and Adipocyte Tissue Macrophage infiltration (ATM). All these pathologies are characterized by increase in reactive oxygen species (ROS) and in proinflammatory cytokines that have been shown to favor the migration of immune cells, particularly of macrophages, in metabolically active organs like the liver and adipose tissue, that in Drosophila are constituted by a unique organ: the fat body. This study, using a unique Drosophila model that mimics human ATM, reveals the beneficial effects of flavonoids to reduce tissue inflammation. Our data show that anthocyanin-rich food reduces the number of hemocytes, Drosophila macrophages, infiltrating the fat cells, a process that is associated with reduced production of ROS and reduced activation of the JNK/SAPK p46 stress kinase, suggesting a fundamental function for anthocyanins as antioxidants in chronic inflammation and in metabolic diseases.

BackgroundNeuronal death is often caused by an excess of glutamate that is maintained at physiological level by a non-autonomous cycle between glia and neurons called the glutamate-glutamine cycle. AimsIt is possible to manipulate the activity of the enzymes that regulate the glutamate-glutamine cycle to ameliorate neuronal death? To answer this question we are taking advantage of Drosophila models used to dissect the cellular and molecular events of neurodegenerative disorders. Glutamate removal from the synaptic cleft by neuroglia is reduced in mouse models of Huntington’s disease (HD) and in HD patients. ResultsOur genetic and biochemical data suggest a key function for the enzyme Glutamine Synthetase-1 in ameliorating animal motility and neuronal loss in a Drosophila model for HD by inducing autophagy, a physiological process necessary to keep the neurons healthy by cleaning them from cellular debris and Huntingtin-protein aggregates. MethodsWe are using genetic and biochemical assays to understand how the metabolic components of the glutamate and glutamine catabolism, which are regulated by the activity of the enzymes Glutamine Synthetase, Glutamine Dehydrogenase and Glutaminase, affects autophagy in neuronal and glial cells, in normal and pathological conditions. In addition, we are preforming feeding experiments to understand if the assimilation of glutamine and glutamate might affect the viability and survival of the animals using a Drosophila model for HD.ConclusionsOur preliminary results show that glutamine in the food increases animal life-span, both in wild-type and HD animals, while glutamate has the opposite effect.

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