21st Century Cardio-Oncology

Abstract

Cardiotoxicity is a well-established complication of oncology therapies. Cardiomyopathy resulting from anthracyclines is a classic example. In the past decade, an explosion of novel cancer therapies, often targeted and more specific than traditional therapies, has revolutionized oncology therapy and dramatically changed cancer prognosis. However, some of these therapies have introduced an assortment of cardiovascular (CV) complications. At times, these devastating outcomes have only become apparent after drug approval and have limited the use of potent therapies. There is a growing need for better testing platforms, both for CV toxicity screening, as well as for elucidating mechanisms of cardiotoxicities of approved cancer therapies. This review discusses the utility of nonclinical models (in vitro, in vivo, & in silico) available and highlights recent advancements in modalities like human stem cell-derived cardiomyocytes for developing more comprehensive cardiotoxicity testing and new means of cardioprotection with targeted anticancer therapies.

Teaching the basics of the mechanism of doxorubicin-induced cardiotoxicity: Have we been barking up the wrong tree?

“…Clearly, the tremendous advances made in new drug discovery and treatment modalities are extending and saving lives. Although this is welcome news, many cancer survivors develop cardiomyopathy (heart muscle dysfunction) years after treatment that undoubtedly decreases the quality of life and often causes life-threatening problems [2]. The side effects from cytotoxic and radiation therapies used to treat cancer cause cardiovascular problems and, in many instances, mortality in cancer survivors stems from such cardiovascular complications [3].…”

Cardio-Oncology: Vascular and Metabolic Perspectives: A Scientific Statement From the American Heart Association

“…As the number of small-molecule kinase inhibitors, which can target multiple kinases, expands, it will be important to define the “off-target” kinase effects of these therapies to better predict possible toxicities when these agents are being tested in humans. 215,216 Understanding the vascular sequelae of new targeted cancer therapies also offers an opportunity for basic and translational investigations in which pathways critical for vascular signaling may be uncovered. 2 Consequently, robust programs in cardio-oncology engage in a multidisciplinary approach in which cardiovascular and oncology teams informed of the most recent research findings closely collaborate to scrutinize for new vascular sequelae and strive to tailor therapies accordingly.…”

“…As the fi of cardio-oncology matures, integration of basic and translational research teams will be needed to most efficiently define the cardiovascular implications of new therapies, to elucidate the mechanisms of toxicity, and to develop management strategies for patients. 215 More robust basic and translational research models, however, will be needed to determine the mechanisms of toxicity. In cardiomyocyte biology, the introduction of induced pluripotent stem cells differentiated into cardiomyocytes offers a human-based platform on which cardiac toxicity can be modeled.…”

The mRNA expression of Il6 and Pdcd1 are predictive and protective factors for doxorubicin‑induced cardiotoxicity

“…Both acute and chronic toxicity may lead to cardiac dysfunction or cardiomyopathy, eventually leading to severe heart failure and death ( 40 , 41 ). While acute cardiotoxicity following treatment with a high dose of DOX is now rare ( 40 ), late-onset chronic cardiotoxicity induced by the cumulative DOX dose remains common, occurring in up to 65% of patients ( 42 ). In the present study, we used a chronic cardiotoxicity model, in which DICT was established in mouse by repeated administration of DOX.…”