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      Drosophila melanogaster: A Model Organism to Study Cancer

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          Abstract

          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.

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            The Hallmarks of Cancer

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              Cancer-related inflammation.

              The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                01 March 2019
                2019
                : 10
                : 51
                Affiliations
                [1] 1Department of Cellular, Computational and Integrative Biology, University of Trento , Trento, Italy
                [2] 2Department of Pharmacy and Biotechnology, University of Bologna , Bologna, Italy
                [3] 3Department of Biosciences, University of Milan , Milan, Italy
                [4] 4Department of Medicine, NYU Langone Medical Center , New York, NY, United States
                Author notes

                Edited by: Maria Grazia Giansanti, Consiglio Nazionale Delle Ricerche (CNR), Italy

                Reviewed by: Alysia Vrailas-Mortimer, Illinois State University, United States; Fiammetta Vernì, Sapienza University of Rome, Italy

                *Correspondence: Paola Bellosta paola.bellosta@ 123456unitn.it

                This article was submitted to Genetic Disorders, a section of the journal Frontiers in Genetics

                Article
                10.3389/fgene.2019.00051
                6405444
                30881374
                5acedce9-8d5e-4f84-88cb-e8f8d540cb76
                Copyright © 2019 Mirzoyan, Sollazzo, Allocca, Valenza, Grifoni and Bellosta.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 September 2018
                : 21 January 2019
                Page count
                Figures: 3, Tables: 0, Equations: 0, References: 216, Pages: 16, Words: 15496
                Funding
                Funded by: Fondazione Cariplo 10.13039/501100002803
                Award ID: 2014703
                Categories
                Genetics
                Review

                Genetics
                drosophila cancer modeling,cancer biology,oncogene,tumor suppressor,tissue growth,signaling,metabolism,therapeutic approaches

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