{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:17:18Z","timestamp":1789503438390,"version":"build-2803163510"},"reference-count":254,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development and Innovation Office of Hungary: Research Excellence Program TKP within the framework of the Therapeutic Development thematic program of the Semmelweis University; National Heart Laboratory","award":["RRF-2.3.1-21-2022-00003"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00003"]}]},{"name":"National Research, Development and Innovation Office of Hungary: Research Excellence Program TKP within the framework of the Therapeutic Development thematic program of the Semmelweis University; National Heart Laboratory","award":["268555672\u2014SFB 1213"],"award-info":[{"award-number":["268555672\u2014SFB 1213"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["RRF-2.3.1-21-2022-00003"],"award-info":[{"award-number":["RRF-2.3.1-21-2022-00003"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["268555672\u2014SFB 1213"],"award-info":[{"award-number":["268555672\u2014SFB 1213"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myocardial protection against ischemia\/reperfusion injury (IRI) is mediated by various ligands, activating different cellular signaling cascades. These include classical cytosolic mediators such as cyclic-GMP (c-GMP), various kinases such as Phosphatydilinositol-3- (PI3K), Protein Kinase B (Akt), Mitogen-Activated-Protein- (MAPK) and AMP-activated (AMPK) kinases, transcription factors such as signal transducer and activator of transcription 3 (STAT3) and bioactive molecules such as vascular endothelial growth factor (VEGF). Most of the aforementioned signaling molecules constitute targets of anticancer therapy; as they are also involved in carcinogenesis, most of the current anti-neoplastic drugs lead to concomitant weakening or even complete abrogation of myocardial cell tolerance to ischemic or oxidative stress. Furthermore, many anti-neoplastic drugs may directly induce cardiotoxicity via their pharmacological effects, or indirectly via their cardiovascular side effects. The combination of direct drug cardiotoxicity, indirect cardiovascular side effects and neutralization of the cardioprotective defense mechanisms of the heart by prolonged cancer treatment may induce long-term ventricular dysfunction, or even clinically manifested heart failure. We present a narrative review of three therapeutic interventions, namely VEGF, proteasome and Immune Checkpoint inhibitors, having opposing effects on the same intracellular signal cascades thereby affecting the heart. Moreover, we herein comment on the current guidelines for managing cardiotoxicity in the clinical setting and on the role of cardiovascular confounders in cardiotoxicity.<\/jats:p>","DOI":"10.3390\/ijms232214121","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T02:24:53Z","timestamp":1668565493000},"page":"14121","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Myocardial Protection and Current Cancer Therapy: Two Opposite Targets with Inevitable Cost"],"prefix":"10.3390","volume":"23","author":[{"given":"Panagiotis","family":"Efentakis","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Andreadou","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos E.","family":"Iliodromitis","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology and Electrophysiology, Evangelical Hospital Hagen-Haspe, 58135 Hagen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6433-4016","authenticated-orcid":false,"given":"Filippos","family":"Triposkiadis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital of Larissa, 41221 Larisa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Ferdinandy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Semmelweis University, 1089 Budapest, Hungary"},{"name":"Pharmahungary Group, 6722 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3017-0476","authenticated-orcid":false,"given":"Rainer","family":"Schulz","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Justus Liebig University Giessen, 35390 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstathios K.","family":"Iliodromitis","sequence":"additional","affiliation":[{"name":"Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1161\/CIRCULATIONAHA.120.053315","article-title":"From Studying Heart Disease and Cancer Simultaneously to Reverse Cardio-Oncology","volume":"144","year":"2021","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4229","DOI":"10.1093\/eurheartj\/ehac244","article-title":"2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS)","volume":"43","author":"Lyon","year":"2022","journal-title":"Eur. 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