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The three traditional modalities of cancer treatment are surgery, radiotherapy, and conventional chemotherapy, and the two modern modalities include molecularly targeted therapy (the fourth modality) and immunotherapy (the fifth modality). The cardiotoxicity associated with conventional chemotherapy and radiotherapy is well known. Similar adverse cardiac events are resurging with the fourth modality. Aside from the conventional and newer targeted agents, even the most newly developed, immune\u2010based therapeutic modalities of anticancer treatment (the fifth modality), e.g., immune checkpoint inhibitors and chimeric antigen receptor (CAR) T\u2010cell therapy, have unfortunately led to potentially lethal cardiotoxicity in patients. Cardiac complications represent unresolved and potentially life\u2010threatening conditions in cancer survivors, while effective clinical management remains quite challenging. As a consequence, morbidity and mortality related to cardiac complications now threaten to offset some favorable benefits of modern cancer treatments in cancer\u2010related survival, regardless of the oncologic prognosis. This review focuses on identifying critical research\u2010practice gaps, addressing real\u2010world challenges and pinpointing real\u2010time insights in general terms under the context of clinical cardiotoxicity induced by the fourth and fifth modalities of cancer treatment. The information ranges from basic science to clinical management in the field of cardio\u2010oncology and crosses the interface between oncology and onco\u2010pharmacology. The complexity of the ongoing clinical problem is addressed at different levels. A better understanding of these research\u2010practice gaps may advance research initiatives on the development of mechanism\u2010based diagnoses and treatments for the effective clinical management of cardiotoxicity.<\/jats:p>","DOI":"10.1002\/med.21463","type":"journal-article","created":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T07:06:41Z","timestamp":1504249601000},"page":"325-376","source":"Crossref","is-referenced-by-count":83,"title":["Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research\u2010practice gaps, challenges, and insights"],"prefix":"10.1002","volume":"38","author":[{"given":"Ping\u2010Pin","family":"Zheng","sequence":"first","affiliation":[{"name":"Cardio\u2010Oncology Research Group Erasmus Medical Center Rotterdam the Netherlands"},{"name":"Department of Pathology Erasmus Medical Center Rotterdam the 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