{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:12:29Z","timestamp":1760235149388,"version":"build-2065373602"},"reference-count":62,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Personalized medicine incorporates genetic information into medical practice so as to optimize the management of chronic diseases. In rare diseases, such as heart cancer (incidence 0.0017\u20130.33%), this may be elusive. Ninety-five percent of the cases are due to secondary involvementwith the neoplasm originating in the lungs, breasts, kidney, blood, or skin. The clinical manifestations of heart tumors (benign or malignant) include heart failure, hypertension, and cardiac arrhythmias of varying severity, frequently resulting in blood vessel emboli, including strokes. This study aims to explain the pathophysiology and contribute to a P4 medicine model for use by cardiologists, pathologists, and oncologists. We created six gene\/protein heart-related and tumor-related targets high-confidence interactomes, which unfold the main pathways that may lead to cardiac diseases (heart failure, hypertension, coronary artery disease, arrhythmias), i.e., the sympathetic nervous system, the renin-angiotensin-aldosterone axis and the endothelin pathway, and excludes others, such as the K oxidase or cytochrome P450 pathways. We concluded that heart cancer patients could be affected by beta-adrenergic blockers, ACE inhibitors, QT-prolonging antiarrhythmic drugs, antibiotics, and antipsychotics. Interactomes may elucidate unknown pathways, adding to patient\/survivor wellness during\/after chemo- and\/or radio-therapy.<\/jats:p>","DOI":"10.3390\/cancers13153882","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T21:51:07Z","timestamp":1627854667000},"page":"3882","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Interactions Networks for Primary Heart Sarcomas"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1227-5274","authenticated-orcid":false,"given":"Styliani A.","family":"Geronikolou","sequence":"first","affiliation":[{"name":"Clinical, Translational and Experimental Surgery Research Centre, Biomedical Research Foundation Academy of Athens, 4, Soranou Ephessiou Str., 11527 Athens, Greece"},{"name":"University Research Institute of Maternal and Child Health & Precision Medicine, National and Kapodistrian University of Athens, Aghia Sophia Children\u2019s Hospital, 11527 Athens, Greece"},{"name":"UNESCO Chair on Adolescent Health Care, National and Kapodistrian University of Athens, Aghia Sophia Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0815-3808","authenticated-orcid":false,"given":"Athanasia","family":"Pavlopoulou","sequence":"additional","affiliation":[{"name":"Izmir Biomedicine and Genome Center (IBG), Balcova, Izmir 35340, Turkey"},{"name":"Izmir International Biomedicine and Genome Institute, Balcova, Izmir 35340, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3098-5264","authenticated-orcid":false,"given":"George P.","family":"Chrousos","sequence":"additional","affiliation":[{"name":"Clinical, Translational and Experimental Surgery Research Centre, Biomedical Research Foundation Academy of Athens, 4, Soranou Ephessiou Str., 11527 Athens, Greece"},{"name":"University Research Institute of Maternal and Child Health & Precision Medicine, National and Kapodistrian University of Athens, Aghia Sophia Children\u2019s Hospital, 11527 Athens, Greece"},{"name":"UNESCO Chair on Adolescent Health Care, National and Kapodistrian University of Athens, Aghia Sophia Children\u2019s Hospital, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis V.","family":"Cokkinos","sequence":"additional","affiliation":[{"name":"Clinical, Translational and Experimental Surgery Research Centre, Biomedical Research Foundation Academy of Athens, 4, Soranou Ephessiou Str., 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,1]]},"reference":[{"key":"ref_1","first-page":"354","article-title":"The concept of disease: From Newton back to Aristotle","volume":"54","author":"Wulff","year":"1999","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1161\/CIRCRESAHA.117.310782","article-title":"Emerging Role of Precision Medicine in Cardiovascular Disease","volume":"122","author":"Leopold","year":"2018","journal-title":"Circ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1142\/S2339547818300020","article-title":"The growing role of precision and personalized medicine for cancer treatment","volume":"6","author":"Krzyszczyk","year":"2018","journal-title":"Technology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s10741-009-9138-x","article-title":"Systems biology and heart failure: Concepts, methods, and potential research applications","volume":"15","author":"Adams","year":"2010","journal-title":"Heart Fail. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.2174\/1389450117666160703162111","article-title":"Cardiac Tumors: Clinical Perspective and Therapeutic Considerations","volume":"18","author":"Ren","year":"2017","journal-title":"Curr. Drug Targets"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1097\/00000658-198002000-00001","article-title":"Primary cardiac tumors","volume":"191","author":"Silverman","year":"1980","journal-title":"Ann. Surg."},{"key":"ref_7","unstructured":"Burke, A., and Virmani, R. (1996). Classification and Incidence of Cardiac Tumors. Tumors of the Heart and Great Vessels, Armed Forces Institute of Pathology."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s11748-018-0912-3","article-title":"Comprehensive review of the epidemiology and treatments for malignant adult cardiac tumors","volume":"66","author":"Taguchi","year":"2018","journal-title":"Gen. Thorac. Cardiovasc. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1758835920918492","DOI":"10.1177\/1758835920918492","article-title":"Genetic aberrations and molecular biology of cardiac sarcoma","volume":"12","author":"Urbini","year":"2020","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1046\/j.1365-2559.1999.00636.x","article-title":"Primary cardiac sarcomas: An immunohistochemical and grading study with long-term follow-up of 24 cases","volume":"34","author":"Donsbeck","year":"1999","journal-title":"Histopathology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"407","DOI":"10.2165\/00129784-200303060-00004","article-title":"Cancer of the heart: Epidemiology and management of primary tumors and metastases","volume":"3","author":"Sarjeant","year":"2003","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"D733","DOI":"10.1093\/nar\/gkv1189","article-title":"Reference sequence (RefSeq) database at NCBI: Current status, taxonomic expansion, and functional annotation","volume":"44","author":"Wright","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1002\/ejhf.1858","article-title":"Epidemiology of heart failure","volume":"22","author":"Groenewegen","year":"2020","journal-title":"Eur. J. Heart Fail."},{"key":"ref_14","unstructured":"Geronikolou, S., Pavlopoulou, A., Chrousos, G.P., and Cokkinos, D.V. (2018). Heart Failure Due to Cardiac Cancer (HFCC1) Signalisome Guides Personalized Cardiotherapy, ESC."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Geronikolou, S., Pavlopoulou, A., Chrousos, G.P., and Cokkinos, D.V. (2018). P3502 A novel interactome to guide therapy and avoid heart failure in cardiac cancer patients\u2013figshare. Eur. Heart J., 39.","DOI":"10.1093\/eurheartj\/ehy563.P3502"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/1756-9966-29-114","article-title":"Oncogenic role of the chromobox protein CBX7 in gastric cancer","volume":"29","author":"Zhang","year":"2010","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7579","DOI":"10.1038\/sj.onc.1208931","article-title":"Defining the oncogenic function of the TEL\/AML1 (ETV6\/RUNX1) fusion protein in a mouse model","volume":"24","author":"Fischer","year":"2005","journal-title":"Oncogene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.3390\/ijms21062011","article-title":"The Fibroblast Growth Factor Receptors in Breast Cancer: From Oncogenesis to Better Treatments","volume":"21","author":"Navid","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref_19","first-page":"766","article-title":"LINC00467 promotes proliferation and invasion in glioma via interacting with miRNA-485-5p","volume":"24","author":"Jiang","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1038\/onc.2013.157","article-title":"Matrix metalloprotease 1a deficiency suppresses tumor growth and angiogenesis","volume":"33","author":"Foley","year":"2014","journal-title":"Oncogene"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"115370","DOI":"10.18632\/oncotarget.23265","article-title":"GRAM domain-containing protein 1B (GRAMD1B), a novel component of the JAK\/STAT signaling pathway, functions in gastric carcinogenesis","volume":"8","author":"Khanna","year":"2017","journal-title":"Oncotarget"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.2147\/COPD.S168772","article-title":"ACE gene polymorphism is associated with COPD and COPD with pulmonary hypertension: A meta-analysis","volume":"13","author":"Ma","year":"2018","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1080\/10641963.2016.1235177","article-title":"Endothelial nitric oxide synthase gene single nucleotide polymorphisms and the risk of hypertension: A meta-analysis involving 63,258 subjects","volume":"39","author":"Xie","year":"2017","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.2174\/1573403X09666131117170446","article-title":"Genetics and heart failure: A concise guide for the clinician","volume":"11","author":"Skrzynia","year":"2015","journal-title":"Curr. Cardiol. Rev."},{"key":"ref_25","first-page":"151","article-title":"Pathophysiology of endothelin and medical emergencies","volume":"45","author":"Bruno","year":"2003","journal-title":"Panminerva Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.ejmg.2010.03.008","article-title":"Mutations in the cardiac transcription factor GATA4 in patients with lone atrial fibrillation","volume":"53","author":"Posch","year":"2010","journal-title":"Eur. J. Med. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1161\/01.CIR.0000102968.19341.FC","article-title":"Effect of atrial fibrillation on hematopoietic progenitor cells: A novel pathophysiological role of the atrial natriuretic peptide?","volume":"108","author":"Goette","year":"2003","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.3389\/fimmu.2019.01130","article-title":"Notch Signaling Regulates Immune Responses in Atherosclerosis","volume":"10","author":"Fortini","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_29","first-page":"699","article-title":"Activation of MMP-2 as a key event in oxidative stress injury to the heart","volume":"14","author":"Ali","year":"2009","journal-title":"Front. Biosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"904","DOI":"10.3389\/fphar.2018.00904","article-title":"New Insights in Cardiac \u03b2-Adrenergic Signaling During Heart Failure and Aging","volume":"9","author":"Eguchi","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1002\/stem.128","article-title":"A complex role for FGF-2 in self-renewal, survival, and adhesion of human embryonic stem cells","volume":"27","author":"Eiselleova","year":"2009","journal-title":"Stem Cells"},{"key":"ref_32","first-page":"s3","article-title":"Role of von Willebrand factor in the haemostasis","volume":"9","author":"Peyvandi","year":"2011","journal-title":"Blood Transfus."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1038\/sj.leu.2402620","article-title":"CD34(+) or CD34(-): Which is the more primitive?","volume":"16","author":"Engelhardt","year":"2002","journal-title":"Leukemia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1530\/JOE-14-0126","article-title":"Increased serum CXCL1 and CXCL5 are linked to obesity, hyperglycemia, and impaired islet function","volume":"222","author":"Nunemaker","year":"2014","journal-title":"J. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4276","DOI":"10.1038\/s41467-019-12152-2","article-title":"NPC1 regulates ER contacts with endocytic organelles to mediate cholesterol egress","volume":"10","author":"Burgoyne","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1097\/PAS.0000000000000184","article-title":"Intimal sarcoma is the most frequent primary cardiac sarcoma: Clinicopathologic and molecular retrospective analysis of 100 primary cardiac sarcomas","volume":"38","author":"Neuville","year":"2014","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_37","first-page":"807","article-title":"A primary cardiac leiomyosarcoma with mutation at H-ras codon 12","volume":"4","author":"Parissis","year":"1997","journal-title":"Oncol. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1111\/bph.15080","article-title":"Restoration of HDAC2 and Nrf2 by andrographolide overcomes corticosteroid resistance in chronic obstructive pulmonary disease","volume":"177","author":"Liao","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6490","DOI":"10.1002\/jcb.27940","article-title":"Identification of key lncRNAs in the carcinogenesis and progression of colon adenocarcinoma by co-expression network analysis","volume":"120","author":"Jiang","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.urolonc.2009.03.018","article-title":"The expression of syndecan-1 and -2 is associated with Gleason score and epithelial-mesenchymal transition markers, E-cadherin and beta-catenin, in prostate cancer","volume":"28","author":"Contreras","year":"2010","journal-title":"Urol. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Bergenfelz, C., Larsson, A.M., von Stedingk, K., Gruvberger-Saal, S., Aaltonen, K., Jansson, S., Jernstrom, H., Janols, H., Wullt, M., and Bredberg, A. (2015). Systemic Monocytic-MDSCs Are Generated from Monocytes and Correlate with Disease Progression in Breast Cancer Patients. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127028"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kugelmann, D., Waschke, J., and Radeva, M.Y. (2015). Adducin is involved in endothelial barrier stabilization. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126213"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1021\/acschembio.9b00338","article-title":"Procaspase-3 Overexpression in Cancer: A Paradoxical Observation with Therapeutic Potential","volume":"14","author":"Boudreau","year":"2019","journal-title":"ACS Chem. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Sobhani, N., D\u2019Angelo, A., Pittacolo, M., Roviello, G., Miccoli, A., Corona, S.P., Bernocchi, O., Generali, D., and Otto, T. (2019). Updates on the CDK4\/6 Inhibitory Strategy and Combinations in Breast Cancer. Cells, 8.","DOI":"10.20944\/preprints201902.0245.v1"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"14140","DOI":"10.1016\/S0021-9258(19)45356-8","article-title":"Evidence for a modified pathway of linoleate degradation. Metabolism of 2,4-decadienoyl coenzyme A","volume":"257","author":"Cuebas","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1126\/science.1096502","article-title":"High frequency of mutations of the PIK3CA gene in human cancers","volume":"304","author":"Samuels","year":"2004","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"7309","DOI":"10.1158\/0008-5472.CAN-14-1354","article-title":"ISG15 is a critical microenvironmental factor for pancreatic cancer stem cells","volume":"74","author":"Sainz","year":"2014","journal-title":"Cancer Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e1697","DOI":"10.1038\/cddis.2015.58","article-title":"Homology and enzymatic requirements of microhomology-dependent alternative end joining","volume":"6","author":"Sharma","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3892\/br.2016.579","article-title":"Association of the nibrin gene (NBN) variants with breast cancer","volume":"4","author":"Uzunoglu","year":"2016","journal-title":"Biomed. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1007\/s001250100650","article-title":"NGF-withdrawal induces apoptosis in pancreatic beta cells in vitro","volume":"44","author":"Pierucci","year":"2001","journal-title":"Diabetologia"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ganjei-Azar, P. (2007). Color. Atlas of Immunocytochemistry in Diagnostic Cytology, Springer Science+Business Media, LLC.","DOI":"10.1007\/978-0-387-32122-6"},{"key":"ref_52","unstructured":"Consortium, T.C.D. (2013). Coronary artery disease risk loci identified in over 190,000 individuals implicate lipid metabolism and inflammation as key causal pathways. Nat. Genet., 25\u201333."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/HCO.0000000000000056","article-title":"Pharmacogenetics of Heart Failure","volume":"29","author":"Mestroni","year":"2014","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.pharmthera.2012.01.002","article-title":"Pharmacogenetic targeting of drugs for heart failure","volume":"134","author":"Bristow","year":"2012","journal-title":"Pharmacol. Ther."},{"key":"ref_55","unstructured":"Fuster, V., Walsh, R.A., and Harrington, R.A. (2011). Dilated Cardiomyopathies in Hurst\u2019s the Heart, The McGraw-Hill Companies, Inc.. [13th ed.]."},{"key":"ref_56","first-page":"441","article-title":"The 2015 WHO Classification of Tumors of the Heart and Pericardium","volume":"11","author":"Burke","year":"2016","journal-title":"J. Thorac. Oncol. Off. Publ. Int. Assoc. Study Lung Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.clon.2007.06.009","article-title":"Malignant tumours of the heart: A review of tumour type, diagnosis and therapy","volume":"19","author":"Kim","year":"2007","journal-title":"Clin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1097\/PAS.0000000000000410","article-title":"Molecular characterization of apocrine salivary duct carcinoma","volume":"39","author":"Chiosea","year":"2015","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1007\/s12105-013-0506-4","article-title":"HRAS mutations in epithelial-myoepithelial carcinoma","volume":"8","author":"Chiosea","year":"2014","journal-title":"Head Neck Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1038\/s41467-019-09177-y","article-title":"Network-based prediction of protein interactions","volume":"10","author":"Luck","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.cell.2011.02.016","article-title":"Interactome networks and human disease","volume":"144","author":"Vidal","year":"2011","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: Protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/15\/3882\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:38:47Z","timestamp":1760164727000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/15\/3882"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,1]]},"references-count":62,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["cancers13153882"],"URL":"https:\/\/doi.org\/10.3390\/cancers13153882","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2021,8,1]]}}}