Myocardial Protection and Current Cancer Therapy: Two Opposite Targets with Inevitable Cost

• Published in: International journal of molecular sciences Vol. 23; no. 22; p. 14121
• Main Authors: Efentakis, Panagiotis, Andreadou, Ioanna, Iliodromitis, Konstantinos E, Triposkiadis, Filippos, Ferdinandy, Péter, Schulz, Rainer, Iliodromitis, Efstathios K
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15.11.2022; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; Adaptive immunity; AKT protein; Angiogenesis; anticancer therapies; Antineoplastic Agents - adverse effects; Cancer therapies; Carcinogenesis; Carcinogens; cardio-oncology; cardioprotection; Cardiotoxicity; Cell growth; Congestive heart failure; Cytokines; Dendritic cells; Drug-Related Side Effects and Adverse Reactions - complications; Drugs; Endothelium; Growth factors; Heart attacks; Heart failure; Homeostasis; Humans; Hypertension; Immune checkpoint inhibitors; Immunological tolerance; Immunosuppressive agents; Inflammation; Ischemia; Kinases; MAP kinase; molecular signaling; myocardial infarction; Myocardium - pathology; Myocytes, Cardiac; Neoplasms - drug therapy; Nitric oxide; Oxidative stress; Physiology; Proteasomes; Proteins; Reperfusion; Review; Side effects; Signal transduction; Stat3 protein; Therapeutic applications; Transcription factors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; Ventricle; cardioprotection; molecular signaling; cardio-oncology; anticancer therapies; myocardial infarction
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232214121

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.