Table 1 Functional and clinical characterization of drugs affecting CVS system
From: An integrative review of nonobvious puzzles of cellular and molecular cardiooncology
Mechanism(s) of anti-cancer activity | Group | Drug | Primary use | CVS disorder/dysfunction |
|---|---|---|---|---|
Inhibition of DNA and RNA synthesis by intercalation between base pairs, inhibition of topoisomerase II, an impairment of DNA repair, ROS-induced DNA damage [13] | Anthracyclines | Doxorubicin | ALL, bladder cancer, breast cancer, Ewing sarcoma, endometrial carcinoma, lymphoma, multiple myeloma, hepatocellular cancer, HL, NHL, SCLC, Waldenström macroglobulinemia, osteosarcoma, thymoma. soft-tissue sarcoma, uterine sarcoma [15] | HF, cardiomyopathy, arrhythmias, pericarditis, myocarditis, ventricular arrhythmias, sinus tachycardia, heart block, ECG changes (nonspecific ST and T, decreased QRS voltage, prolongation of QT interval), palpitations [15, 251, 501] |
Daunorubicin | AML, ALL [502] | ECG changes (nonspecific ST and T, decreased QRS, prolongation of QT interval), LVF, myocarditis [251, 503] | ||
Epirubicin | Gastric cancer, breast cancer, esophageal cancer, osteosarcoma, soft-tissue sarcoma [15] | |||
Idarubicin | AML [15] | HF, arrhythmias, angina, myocardial infarction [13, 15, 251] | ||
DNA damage (cross-linking of DNA strands, impaired base pairing, strand breaks) [505] | Alkylating agents | Busulfan | Essential thrombocythemia, polycythemia vera [15] | HF, palpitations, cardiac tamponade, cardiomegaly, pericardial effusion, hypokinesis of the ventricular apex, ECG changes (flat T waves or peaked P waves) [251] |
Cyclophosphamide | ALL, breast cancer, CLL, Ewing sarcoma, HL, NHL, multiple myeloma, SCLC [15] | Arrhythmias, chest pain, pleural and pericardial effusions, myocarditis, pericarditis, myocardial infarction, cardiac tamponade, HF, ECG changes (loss of QRS voltage) [251, 503, 506] | ||
Ifosfamide | Bladder cancer, cervical cancer, Ewing sarcoma, HL, NHL, osteosarcoma, soft-tissue sarcoma, testicular cancer, thymoma, ovarian cancer [15] | Pleural and pericardial effusions, reentrant ventricular tachycardia, pulseless tachycardia, ECG changes (nonspecific ST and T, loss of QRS voltage) [251] | ||
Melphalan | Multiple myeloma, ovarian cancer, HL, lymphomas [15] | Arrhythmias, atrial fibrillation [15] | ||
Inhibition of DNA replication due to depletion of nucleotides, induction of DNA and RNA strand breaks, induction of apoptosis [13] | Antimetabolites | 5-Fluorouracil | Bladder cancer, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, gastric cancer, hepatobiliary cancer, pancreatic cancer, squamous cell carcinomas [15] | Angina, chest pain, ECG changes (ST-segment changes, T wave abnormalities), palpitation, dyspnea, coronary vasospasm, tachycardia, bradycardia, hypotension, HF, myocardial ischemia [13, 251, 507] |
Capecitabine | Breast cancer, colorectal cancer, gastric cancer, hepatobiliary cancer, esophageal cancer, ovarian cancer, fallopian peritoneal cancer, pancreatic cancer [15] | Chest pain, palpitation, dyspnea, hypotension, tachycardia, bradycardia, hypertension, HF, myocardial ischemia [507, 508] | ||
Gemcitabine | Adenocarcinoma, breast cancer, bladder cancer, cervical cancer, head and neck cancer, hepatobiliary cancer, HL, NHL, malignant pleural mesothelioma, NHL, NSCLC, ovarian cancer, pancreatic cancer, sarcoma, SCLC, testicular cancer, uterine cancer [15] | Coronary vasospasm, capillary leak syndrome, arrhythmias, myocardial ischemia and infarction, LVEF reduction [503, 509, 510] | ||
Taxanes | Paclitaxel | Adenocarcinoma, bladder cancer, breast cancer, cervical cancer, head and neck cancers, Kaposi sarcoma, NSCLC, esophageal and gastric cancer, ovarian cancer, SCLC, soft-tissue sarcoma, testicular germ cell tumor, thymoma [15] | Atrial and ventricular arrhythmias, atrial fibrillation, atrial flutter, atrial tachycardias, sinus bradycardia left bundle branch block, myocardial ischemia [13, 15, 251] | |
Docetaxel | Adenocarcinoma, bladder cancer, breast cancer, Ewing sarcoma, head and neck cancer, NSCLC, esophageal and gastric cancer, ovarian cancer, prostate cancer, SCLC, soft-tissue sarcoma [15] | Arrhythmias, atrial fibrillation, atrial flutter, atrial tachycardias, bradycardia, ECG changes (QT prolongation) [13, 501, 503] | ||
Inhibition of microtubule formation in mitotic spindle [512, 513] | Alkaloids | Vinblastine | Bladder cancer, HL, melanoma, NSCLC, soft-tissue sarcoma, testicular cancer [15] | Myocardial ischemia [514] |
Vincristine | ALL, HL, NHL, Ewing sarcoma, gestational trophoblastic tumor, multiple myeloma, ovarian cancer, primary CNS lymphoma, SCLC, thymoma [15] | Myocardial infraction; myocardial ischemia, ECG changes (T wave inversions, ST segment depression), atrial fibrillation, LVF [251, 503] | ||
Binding and cross-linking within DNA, preventing its replication, induction of apoptosis [515] | Platins | Cisplatin | Bladder cancer, breast cancer, cervical cancer, endometrial carcinoma, esophageal and gastric cancer, head and neck cancer, HL, malignant pleural mesothelioma, multiple myeloma, NHL, osteosarcoma, ovarian cancer, penile cancer, SCLC, testicular cancer [15] | HF, arrhythmias, interventricular block myocardial infraction, hypotension, ECG changes (ST-T wave, T wave inversion) [251] |
Oxaliplatin | Biliary adenocarcinoma, CLL, colorectal cancer, neuroendocrine tumor (carcinoid), NHL, ovarian cancer, esophageal/gastric cancer, pancreatic cancer, testicular cancer [15] | Arrhythmias [15] | ||
Antitumor antibiotics | Bleomycin | HL, testicular cancer, ovarian germ cell cancer [15] | ||
Induction of apoptosis, inhibition of angiogenesis [519] | Immunomodulatory drugs | Lenalidomide | CLL, diffuse large B cell lymphoma, MCL, multiple myeloma, MDS [15] | Arterial thromboembolism disease, myocardial infraction, cerebral vascular events, deep vein thrombosis, pulmonary embolism [520] |
Inhibition of HER2 tyrosine kinase [13] | Humanized monoclonal antibodies | Trastuzumab | Breast cancer, gastric cancer [15] | HF, myocardial necrosis/fibrosis, LVEF decline, HF, LFV [503, 521] |
Inhibition of VEGFR kinases [522] | Multi-target kinase inhibitors | Lenvatinib | Hepatocellular cancer, renal cell carcinoma, thyroid cancer [15] | Hypertension, HF, ECG changes (QT interval prolongation) [523, 524] |
Pazopanib | Renal cell carcinoma, soft-tissue carcinoma, thyroid cancer [15] | HF, LVEF reduction [525] | ||
Vandetanib | Thyroid cancer [15] | HF, tachycardia, palpitation, ECG changes (QT prolongation), LVEF reduction [524] | ||
Inhibition of proteasomal protein degradation leading to apoptosis and ER stress [526] | Proteasome inhibitors | Bortezomib | Follicular lymphoma, mantle cell lymphoma, multiple myeloma, T-cell lymphoma [15] | HF, coronary heart disease, arrhythmias, thromboembolic disease, pericardial complications, peripheral vascular disease [527] |
Carfilzomib | Multiple myeloma, Waldenström macroglobulinemia [15] | HF, arrhythmias, hypertension, myocardial ischemia [382, 503] | ||
Reactivation of immunosurveillance mechanisms, particularly T-cell activity [455] | Immune checkpoint inhibitors | Ipilimumab (anti-CTLA-4) | Colorectal cancer, melanoma, renal cell carcinoma [455] | |
Nivolumab (anti-PD-1) | Colorectal cancer, hepatocellular carcinoma, HL, melanoma, NSCLC, SCLC, urothelial carcinoma [15] | Arrythmias, peripheral edema, hypertension [15] | ||
Pembrolizumab (anti-PD-1) | Cervical cancer, gastric cancer, hepatocellular carcinoma; HL, melanoma, Merkel cell carcinoma, NSCLC, urothelial carcinoma [15] | Arrythmias, HF, edema, pericarditis, pericardial effusion [15, 528] | ||
Atezolizumab (anti-PD-L1) | Breast cancer (triple negative), NSCLC, SCLC, urothelial carcinoma [15] | Myocardial infarction [528] |