{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:29:12Z","timestamp":1789615752407,"version":"build-2803163510"},"reference-count":70,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT prolongation, torsades de pointes, pericardial effusion, and hypotension, as well as chronic conditions, such as hypertension, and systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovascular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovascular side effect continues even after the causative medication is stopped, it is referred to as a cardiotoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even at very low medication dosages, and can present as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome, and myocarditis caused by cancer therapy.<\/jats:p>","DOI":"10.3390\/life14030400","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T06:58:39Z","timestamp":1710745119000},"page":"400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cardio-Oncoimmunology: Cardiac Toxicity, Cardiovascular Hypersensitivity, and Kounis Syndrome"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9751-6710","authenticated-orcid":false,"given":"Nicholas","family":"Kounis","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Cardiology, University Hospital of Patras, 26500 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6912-7523","authenticated-orcid":false,"given":"Ming-Yow","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan"},{"name":"Taipei Heart Institute, Taipei Medical University, Taipei City 110301, Taiwan"},{"name":"Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei City 110301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3022-266X","authenticated-orcid":false,"given":"Cesare","family":"de Gregorio","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina Medical School, 98122 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Mplani","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Patras University Hospital, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9598-6954","authenticated-orcid":false,"given":"Christos","family":"Gogos","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Papageorgiou General Hospital, Nea Efkarpia, 56403 Thessaloniki, Greece"},{"name":"First University Cardiology Department, AHEPA General Hospital, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6901-3681","authenticated-orcid":false,"given":"Stelios","family":"Assimakopoulos","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Medical School, University of Patras, University Hospital of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5514-7083","authenticated-orcid":false,"given":"Panagiotis","family":"Plotas","sequence":"additional","affiliation":[{"name":"Department of Speech Therapy, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Periklis","family":"Dousdampanis","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Saint Andrews State General Hospital, 26221 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Kouni","sequence":"additional","affiliation":[{"name":"Speech Therapy Practice, Queen Olgas Square, 26221 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-3301","authenticated-orcid":false,"given":"Anastasopoulou","family":"Maria","sequence":"additional","affiliation":[{"name":"Department of Cardiology, General Hospital of Aigio, 25100 Aigio, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2779-0765","authenticated-orcid":false,"given":"Grigorios","family":"Tsigkas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, University Hospital of Patras, 26500 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Koniari","sequence":"additional","affiliation":[{"name":"Cardiology Department, Lancashire Cardiac Center, Blackpool Teaching Hospitals, Blackpool FY3 8NP, UK"},{"name":"Liverpool Center of Cardiovascular Science, Liverpool Heart and Chest Hospital, Liverpool L14 3PE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727487","DOI":"10.3389\/fcvm.2022.727487","article-title":"Cardio-Oncology: A Myriad of Relationships between Cardiovascular Disease and Cancer","volume":"9","author":"Wang","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Palmieri, V., Vietri, M.T., Montalto, A., Montisci, A., Donatelli, F., Coscioni, E., and Napoli, C. (2023). Cardiotoxicity, cardioprotection, and prognosis in survivors of anticancer treatment undergoing cardiac surgery: Unmet needs. Cancers, 15.","DOI":"10.3390\/cancers15082224"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4796","DOI":"10.1093\/eurheartj\/ehad462","article-title":"Association of radiation dose to cardiac substructures with major ischaemic events following breast cancer radiotherapy","volume":"44","author":"Lai","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"847012","DOI":"10.3389\/fcvm.2022.847012","article-title":"Cardiotoxicity of Anticancer Drugs: Molecular Mechanisms and Strategies for Cardioprotection","volume":"9","author":"Morelli","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1002\/ehf2.14034","article-title":"Histopathological and epigenetic changes in myocardium associated with cancer therapy-related cardiac dysfunction","volume":"9","author":"Terada","year":"2022","journal-title":"ESC Heart Fail."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/j.gendis.2023.01.024","article-title":"Immune checkpoint inhibitors break whose heart? Perspectives from cardio-immuno-oncology","volume":"11","author":"He","year":"2023","journal-title":"Genes Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s12094-016-1508-y","article-title":"Evaluation and management of chemotherapy-induced cardiotoxicity in breast cancer: A Delphi study","volume":"19","author":"Gavila","year":"2017","journal-title":"Clin. Transl. Oncol."},{"key":"ref_8","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. Heart J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1111\/all.13226","article-title":"Validation of international consensus equation for acute serum total tryptase in mast cell activation: A perioperative perspective","volume":"72","author":"Baretto","year":"2017","journal-title":"Allergy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.jaip.2018.05.030","article-title":"Kounis syndrome caused by anaphylaxis without skin manifestations after cefazolin administration","volume":"7","author":"Adachi","year":"2019","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13601-017-0144-0","article-title":"Approach to the diagnosis of drug hypersensitivity reactions: Similarities and differences between Europe and North America","volume":"7","author":"Torres","year":"2017","journal-title":"Clin. Transl. Allergy"},{"key":"ref_12","first-page":"e55514K","article-title":"Type III Kounis Syndrome Caused by Iodine Contrast Media After Improvement of Allergic Symptoms","volume":"16","author":"Okuda","year":"2024","journal-title":"Cureus"},{"key":"ref_13","first-page":"1612","article-title":"Is vasospastic angina an inflammatory disease?","volume":"96","author":"Rich","year":"2005","journal-title":"Am. J. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1111\/j.1742-1241.2003.tb10570.x","article-title":"Kounis syndrome secondary to allergic reaction following shellfish ingestion","volume":"57","author":"Zavras","year":"2003","journal-title":"Int. J. Clin. Pract."},{"key":"ref_15","first-page":"e53145","article-title":"Adrenaline, Takotsubo, Anaphylaxis, and Kounis Syndrome (ATAK) Complex Unveiled: Integrating Takotsubo and Kounis Syndromes in the Context of Chemotherapy-Related Anaphylaxis","volume":"16","author":"Puri","year":"2024","journal-title":"Cureus"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"308","DOI":"10.4274\/balkanmedj.galenos.2023.2023-4-96","article-title":"Attack the ATAK. A Challenging Contemporary Complex: Pathophysiologic, Therapeutic, and Preventive Considerations","volume":"40","author":"Kounis","year":"2023","journal-title":"Balkan Med. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1056\/NEJMcpc2300898","article-title":"Case 22-2023: A 59-Year-Old Woman with Hypotension and Electrocardiographic Changes","volume":"389","author":"Szabo","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.ijcard.2011.02.066","article-title":"A case of coronary hypersensitivity (Kounis) syndrome associated with mid-ventricular ballooning pattern, intracoronary thrombosis and troponin elevation","volume":"149","author":"Gori","year":"2011","journal-title":"Int. J. Cardiol."},{"key":"ref_19","first-page":"e44704","article-title":"A Rare Case of Kounis Syndrome Secondary to Infliximab","volume":"15","year":"2023","journal-title":"Cureus"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e58","DOI":"10.1016\/j.jccase.2011.04.004","article-title":"Carboplatin-induced Kounis syndrome","volume":"4","author":"Baroni","year":"2011","journal-title":"J. Cardiol. Cases"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e647","DOI":"10.1097\/MJT.0000000000001027","article-title":"Carboplatin-Induced Kounis Syndrome","volume":"27","author":"Tambe","year":"2020","journal-title":"Am. J. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1016\/j.ijcard.2009.03.104","article-title":"Kounis syndrome in a patient with ovarian cancer and allergy to iodinated contrast media: Report of a case of vasospastic angina induced by chemotherapy","volume":"149","author":"Oneglia","year":"2011","journal-title":"Int. J. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e776","DOI":"10.1200\/JCO.2011.36.4265","article-title":"Oxaliplatin-induced coronary vasospasm manifesting as Kounis syndrome: A case report","volume":"29","author":"Chang","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"18","DOI":"10.21037\/pcm-22-51","article-title":"A challenge in emergency department: A case report of oxaliplatin-induced Kounis syndrome","volume":"6","author":"Albanesi","year":"2023","journal-title":"Precis. Cancer Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.ijcard.2015.10.027","article-title":"Cisplatin-induced bradycardia: Cardiac toxicity or cardiac hypersensitivity and Kounis syndrome?","volume":"202","author":"Kounis","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_26","first-page":"1","article-title":"Type I Kounis syndrome from paclitaxel infusion","volume":"3","author":"Wang","year":"2020","journal-title":"J. Cardiol. Case Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1111\/imj.15226","article-title":"Type 1 Kounis syndrome after paclitaxel infusion in a patient treated for lung adenocarcinoma","volume":"51","author":"Wang","year":"2021","journal-title":"Intern. Med. J."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Narroway, H.G., Katib, N., Gomes, M.L., Varcoe, R.L., and Thomas, S.D. (2020). Kounis Syndrome after Angioplasty of the Superficial Femoral Artery with Paclitaxel-Coated Balloon. Ann. Vasc. Surg., 69.","DOI":"10.1055\/s-0041-1729097"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1024\/0301-1526\/a000604","article-title":"Acute hypersensitivity reaction to femoral drug-coated balloons","volume":"46","author":"Lake","year":"2017","journal-title":"Vasa"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1177\/1078155214563814","article-title":"induced ventricular fibrillation arrest: Possible Kounis syndrome","volume":"22","author":"Kido","year":"2016","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ejro.2019.02.004","article-title":"Kounis syndrome induced by contrast media: A case report and review of literature","volume":"6","author":"Shibuya","year":"2019","journal-title":"Eur. J. Radiol. Open"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1136\/emj.2008.060574","article-title":"Coronary spasm induced by capecitabine mimicks ST elevation myocardial infarction","volume":"25","author":"Scott","year":"2008","journal-title":"Emerg. Med. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1016\/j.ijcard.2007.06.152","article-title":"Capecitabine induced vasospastic angina","volume":"130","author":"Coughlin","year":"2008","journal-title":"Int. J. Cardiol."},{"key":"ref_34","first-page":"320","article-title":"Capecitabine may induce coronary artery vasospasm","volume":"5","author":"Tsiamis","year":"2012","journal-title":"Hellenic J. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"835","DOI":"10.2459\/01.JCM.0000250874.09273.9b","article-title":"A case of acute myocardial infarction during 5-fluorouracil infusion","volume":"7","author":"Canale","year":"2006","journal-title":"J. Cardiovasc. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"E111","DOI":"10.15420\/ahhj.2010.8.2.111","article-title":"Angina induced by 5-fluorouracil infusion in a patient with normal coronaries","volume":"8","author":"Tajik","year":"2010","journal-title":"Am. Heart Hosp. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1177\/0267659111410347","article-title":"Is 5-fluorouracil-induced vasospasm a Kounis syndrome? A diagnostic challenge","volume":"26","author":"Karabay","year":"2011","journal-title":"Perfusion"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1200\/JCO.1990.8.6.1093","article-title":"A phase I clinical trial and pharmacokinetic evaluation of liposome-encapsulated doxorubicin","volume":"8","author":"Rahman","year":"1990","journal-title":"J. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1111\/j.1398-9995.2006.01211.x","article-title":"Simultaneous exposure of several allergens has an additive effect on multisensitized basophils","volume":"61","author":"Nopp","year":"2006","journal-title":"Allergy"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Dupont, M., Carlier, C., Gower-Rousseau, C., Barbier-Lider, P., Botsen, D., Brasseur, M., Burgevin, A., Chourbagi, C., D\u2019Almeida, R., and Hautefeuille, V. (2022). Incidence and associated factors of cetuximab-induced hypersensitivity infusion reactions in 1392 cancer patients treated in four French areas: A possible association with Lyme disease?. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-10192-4"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.crohns.2011.08.001","article-title":"Acute and delayed hypersensitivity reactions to infliximab and adalimumab in a patient with Crohn\u2019s disease","volume":"6","author":"Steenholdt","year":"2012","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e103","DOI":"10.1016\/j.ijcard.2013.12.012","article-title":"Antibodies against biologicals and acute coronary syndromes","volume":"171","author":"Gori","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_43","unstructured":"Brili, S., Bei, E., Kounis, N.G., Chrysohoou, C., Antoniou, C.K., Kontopidou, F., Bonfanti, L., Cervellin, G., Tousoulis, D.T., and Tsioufis, C. (2021). Hypertensive crisis and pulmonary edema following rituximab-induced anaphylaxis. Acta Biomed., 92."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ejca.2022.09.024","article-title":"Incidence and severity of anaphylaxis and hypersensitivity in trials of intravenous pertuzumab plus trastuzumab or the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection for HER2-positive breast cancer","volume":"178","author":"Swain","year":"2023","journal-title":"Eur. J. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9428","DOI":"10.3390\/curroncol29120741","article-title":"Nivolumab Hypersensitivity Reactions a Myth or Reality in Solid Tumors-A Systematic Review of the Literature","volume":"29","author":"Slavu","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_46","first-page":"149","article-title":"Avelumab for Advanced Merkel Cell Carcinoma: Global Real-World Data on Patient Response and Survival","volume":"14","author":"Lohray","year":"2023","journal-title":"Pragmat Obs. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.5858\/arpa.2019-0447-OA","article-title":"Histopathologic Characterization of Myocarditis Associated with Immune Checkpoint Inhibitor Therapy","volume":"144","author":"Sobol","year":"2020","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Engler, R.J.M., Montgomery, J.R., Spooner, C.E., Nelson, M.R., Collins, L.C., Ryan, M.A., Chu, C.S., Atwood, J.E., Hulten, E.A., and Rutt, A.A. (2023). Myocarditis and pericarditis recovery following smallpox vaccine 2002-2016: A comparative observational cohort study in the military health system. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0283988"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9541","DOI":"10.1002\/cam4.5729","article-title":"Association between immune checkpoint inhibitors and myocardial infarction in Asians: A population-based self-controlled case series","volume":"12","author":"Chan","year":"2023","journal-title":"Cancer Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6699","DOI":"10.3390\/curroncol30070491","article-title":"Desensitization Protocol for Cemiplimab-Related Infusion Reaction in Cutaneous Squamous Cell Carcinoma: A Case Report and Literature Review","volume":"30","author":"Banini","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Galateanu, B., Pu\u0219ca\u0219u, A.I., Tircol, S.A., Tanase, B.C., Hudita, A., Negrei, C., Burcea-Dragomiroiu, G.T., Negreanu, L., Vacaroiu, I.A., and Ginghin\u0103, O. (2023). Allergy in Cancer Care: Antineoplastic Therapy-Induced Hypersensitivity Reactions. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043886"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"827446","DOI":"10.3389\/fphar.2022.827446","article-title":"Biomarkers of PEGylated Liposomal Doxorubicin-Induced Hypersensitivity Reaction in Breast Cancer Patients Based on Metabolomics","volume":"13","author":"Zhuang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Liang, H.Z., Zhao, H., Gao, J., Cao, C.F., and Wang, W.M. (2021). Epirubicin-induced Kounis syndrome. BMC Cardiovasc. Disord., 21.","DOI":"10.1186\/s12872-021-01936-4"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Teixeira, C.S.S., and Sousa, S.F. (2021). Current Status of the Use of Multifunctional Enzymes as Anti-Cancer Drug Targets. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14010010"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Jang, J.Y., Kim, D., and Kim, N.D. (2023). Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098457"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s13045-023-01485-7","article-title":"Targeting NEDD8-activating enzyme for cancer therapy: Developments, clinical trials, challenges and future research directions","volume":"16","author":"Fu","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e49","DOI":"10.1016\/j.clcc.2015.05.003","article-title":"Successful Desensitization Protocol for Hypersensitivity Reaction Caused by Irinotecan in a Patient with Metastatic Colorectal Cancer","volume":"14","author":"Hassoun","year":"2015","journal-title":"Clin. Color. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jaapos.2014.09.018","article-title":"Hypersensitivity to sub-Tenon\u2019s topotecan in fibrin adhesive in patients with retinoblastoma","volume":"19","author":"Astudillo","year":"2015","journal-title":"J. Am. Assoc. Pediatr. Ophthalmol. Strabismus"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Grela-Wojewoda, A., Pacholczak-Madej, R., Adamczyk, A., Korman, M., and P\u00fcsk\u00fcll\u00fco\u011flu, M. (2022). Cardiotoxicity Induced by Protein Kinase Inhibitors in Patients with Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052815"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.anai.2017.05.010","article-title":"Desensitization to protein kinase inhibitors: A systematic review","volume":"119","author":"Chillari","year":"2017","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1182\/bloodadvances.2019000268","article-title":"Side-effects profile and outcomes of ponatinib in the treatment of chronic myeloid leukemia","volume":"4","author":"Chan","year":"2020","journal-title":"Blood Adv."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1016\/j.jaci.2022.04.020","article-title":"Tyrosine kinase inhibitors for the treatment of indolent systemic mastocytosis: Are we there yet?","volume":"149","author":"Akin","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/s41392-023-01469-6","article-title":"Adverse effects of tyrosine kinase inhibitors in cancer therapy: Pathophysiology, mechanisms and clinical management","volume":"8","author":"Sharma","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"480650","DOI":"10.5402\/2012\/480650","article-title":"Transcatheter arterial chemoembolization: History for more than 30 years","volume":"2012","author":"Guan","year":"2012","journal-title":"ISRN Gastroenterol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jccase.2015.05.007","article-title":"A case of Kounis syndrome associated with transcatheter arterial chemoembolization for hepatocellular carcinoma","volume":"12","author":"Iyonaga","year":"2015","journal-title":"J. Cardiol. Cases"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4485754","DOI":"10.1155\/2021\/4485754","article-title":"Kounis Syndrome Secondary to Medicine-Induced Hypersensitivity","volume":"2021","author":"Karunathilake","year":"2021","journal-title":"Case Rep. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"364","DOI":"10.18176\/jiaci.0712","article-title":"Hypersensitivity Reactions to Cancer Chemotherapy: Practical Recommendations of ARADyAL for Diagnosis and Desensitization","volume":"31","author":"Vega","year":"2021","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/all.15113","article-title":"Hypersensitivity reactions to chemotherapy: An EAACI Position Paper","volume":"77","author":"Pagani","year":"2022","journal-title":"Allergy"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Barroso, B., G\u00f3mez-L\u00f3pez, A., Betancor, D., Valverde-Monge, M., and Sastre, J. (Allergy, 2024). Reply to \u201cEuropean academy of allergy and clinical immunology, food allergy, anaphylaxis guidelines group. EAACI guidelines: Anaphylaxis (2021 update)\u201d, Allergy, ahead of print.","DOI":"10.1111\/all.16018"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e16","DOI":"10.15420\/ecr.2022.63","article-title":"The 2022 European Society of Cardiology Cardio-oncology Guidelines in Focus","volume":"18","author":"Gent","year":"2023","journal-title":"Eur. Cardiol."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/3\/400\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:15:15Z","timestamp":1760105715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/14\/3\/400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,18]]},"references-count":70,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["life14030400"],"URL":"https:\/\/doi.org\/10.3390\/life14030400","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,18]]}}}