To date, five cancer treatment modalities have been defined. 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‐based therapeutic modalities of anticancer treatment (the fifth modality), e.g., immune checkpoint inhibitors and chimeric antigen receptor (CAR) T‐cell therapy, have unfortunately led to potentially lethal cardiotoxicity in patients. Cardiac complications represent unresolved and potentially life‐threatening 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‐related survival, regardless of the oncologic prognosis. This review focuses on identifying critical research‐practice gaps, addressing real‐world challenges and pinpointing real‐time 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‐oncology and crosses the interface between oncology and onco‐pharmacology. The complexity of the ongoing clinical problem is addressed at different levels. A better understanding of these research‐practice gaps may advance research initiatives on the development of mechanism‐based diagnoses and treatments for the effective clinical management of cardiotoxicity.

中文翻译：

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现代癌症治疗的突破和难以捉摸的心脏毒性：关键的研究实践差距、挑战和见解。

迄今为止，已经定义了五种癌症治疗方式。传统的三种癌症治疗方式是手术、放疗和常规化疗，两种现代方式包括分子靶向治疗（第四种方式）和免疫疗法（第五种方式）。与常规化学疗法和放射疗法相关的心脏毒性是众所周知的。类似的心脏不良事件在第四种模式中再次出现。除了传统的和更新的靶向药物外，即使是最新开发的基于免疫的抗癌治疗方式（第五种方式），例如免疫检查点抑制剂和嵌合抗原受体（CAR）T 细胞疗法，不幸的是导致了对患者有潜在的致命心脏毒性。心脏并发症是癌症幸存者尚未解决且可能危及生命的情况，而有效的临床管理仍然非常具有挑战性。因此，与心脏并发症相关的发病率和死亡率现在有可能抵消现代癌症治疗在癌症相关生存方面的一些有利益处，无论肿瘤学预后如何。这篇综述的重点是确定关键的研究与实践差距，解决现实世界的挑战，并在第四和第五种癌症治疗方式引起的临床心脏毒性的背景下，以一般术语准确指出实时见解。信息范围从基础科学到心脏肿瘤学领域的临床管理，跨越肿瘤学和肿瘤药理学之间的界面。正在进行的临床问题的复杂性在不同层面得到解决。更好地了解这些研究与实践之间的差距，可能会推进基于机制的诊断和治疗发展的研究计划，以有效地临床管理心脏毒性。