Abstract
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.
Highlights
Available cancer treatments include the traditional surgery, radiotherapy, and conventional chemotherapy approaches and have been extended with two new modalities in recent decades: molecularly targeted therapy (MTT) and immunotherapy
The research gaps resulting from the problematic specificity/selectivity of drugs leave a bottleneck on effective clinical management because of uncontrollable toxicities on multiple organs
Improving the specificity/selectivity of drug target selection is considered the single most important factor,[592] and this strategy will substantially minimize the risk of potential cardiovascular safety liabilities and other organ toxicity
Summary
Available cancer treatments include the traditional surgery, radiotherapy, and conventional chemotherapy approaches and have been extended with two new modalities in recent decades: molecularly targeted therapy (MTT) and immunotherapy. Cost savings are a major incentive for the adoption of biosimilars, and some biosimilars have been developed and used in clinical oncology trials.[87,88] Biosimilars refer to biologic products that demonstrate no clinically meaningful differences in terms of quality attributes, efficacy, safety, and immunogenicity compared with an existing licensed, originator biologic.[89] The incorporation of biosimilars into healthcare systems worldwide may result in a 30–45% cost savings.[87] A strategy to prevent clinical cardiotoxicity will have significant impacts on the overall prognosis and survival of cancer patients This strategy is part of the field of cardiovascular safety, with multifaceted aspects at multiple levels involving improvement of preclinical models for the study of chemotherapy-induced cardiotoxicity,[90] appropriate preapproval investigations and monitoring during clinical practice.[91] In addition, it is important to realize that the approval decision following preapproval clinical trials does not necessarily represent a singular moment of clarity about the risks and benefits associated with a drug; continuous post-marketing surveillance and vigilance for cardiotoxicity is required.[91] The research gaps in novel cancer treatment-related cardiotoxicity range from basic, translational, clinical, and epidemiologic sciences to cancer patients, medical professionals, research communities, pharmaceutical industries, regulatory bodies, and research funding agencies. This review focuses on the identification of the current gaps between research and clinical practice and addresses the challenges and pinpoints current insights of clinical cardiotoxicity induced by the fourth and fifth modalities of cancer treatments
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