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      Cancer and pulmonary hypertension: Learning lessons and real-life interplay

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          Abstract

          This article reviews the scientific reasons that support the intriguing vision of pulmonary hypertension (PH) as a disease with a cancer-like nature and to understand whether this point of view may have fruitful consequences for the overall management of PH. This review compares cancer and PH in view of Hanahan and Weinberg’s principles (i.e., hallmarks of cancer) with an emphasis on hyperproliferative, metabolic, and immune/inflammatory aspects of the disease. In addition, this review provides a perspective on the role of transcription factors and chromatin and epigenetic aberrations, besides genetics, as “common driving mechanisms” of PH hallmarks and the foreseeable use of transcription factor/epigenome targeting as multitarget approach against the hallmarks of PH. Thus, recognition of the widespread applicability and analogy of these concepts will increasingly affect the development of new means of PH treatment.

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          Most cited references133

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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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            Comprehensive genomic characterization defines human glioblastoma genes and core pathways

            (2008)
            Human cancer cells typically harbor multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multidimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here, we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas (GBM), the most common type of adult brain cancer, and nucleotide sequence aberrations in 91 of the 206 GBMs. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the PI3 kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of GBM. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
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              Fundamentals of cancer metabolism

              Researchers provide a conceptual framework to understand current knowledge of the fundamentals of cancer metabolism.
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                Author and article information

                Contributors
                Journal
                Glob Cardiol Sci Pract
                Glob Cardiol Sci Pract
                GCSP
                GCSP
                Global Cardiology Science & Practice
                Magdi Yacoub Heart Foundation (UK )
                2305-7823
                30 April 2020
                30 April 2020
                : 2020
                : 1
                : e202010
                Affiliations
                [1 ]Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI) , Bad Nauheim, 61231, Germany
                [2 ]Department of Internal Medicine, Member of the DZL, Member of CPI, Justus Liebig University , Giessen, 35392, Germany
                [3 ]Institute for Lung Health (ILH), Member of the DZL, Justus Liebig University , Giessen, 35392, Germany
                Article
                gcsp.2020.10
                10.21542/gcsp.2020.10
                7590929
                ed8fe5b0-a427-4d57-b9c2-dce41aba4a33
                Copyright ©2020 The Author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution license CC BY 4.0, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 March 2020
                : 30 May 2020
                Categories
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