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Review
. 2021 Jul 28;6(8):705-718.
doi: 10.1016/j.jacbts.2021.05.008. eCollection 2021 Aug.

Cardio-Oncology: Understanding the Intersections Between Cardiac Metabolism and Cancer Biology

Anja Karlstaedt  1   2 , Matthew Barrett  3 , Ray Hu  4 , Seth Thomas Gammons  5 , Bonnie Ky  3   4
Affiliations
Review

Cardio-Oncology: Understanding the Intersections Between Cardiac Metabolism and Cancer Biology

Anja Karlstaedt et al. JACC Basic Transl Sci. .

Abstract

An important priority in the cardiovascular care of oncology patients is to reduce morbidity and mortality, and improve the quality of life in cancer survivors through cross-disciplinary efforts. The rate of survival in cancer patients has improved dramatically over the past decades. Nonetheless, survivors may be more likely to die from cardiovascular disease in the long term, secondary, not only to the potential toxicity of cancer therapeutics, but also to the biology of cancer. In this context, efforts from basic and translational studies are crucial to understanding the molecular mechanisms causal to cardiovascular disease in cancer patients and survivors, and identifying new therapeutic targets that may prevent and treat both diseases. This review aims to highlight our current understanding of the metabolic interaction between cancer and the heart, including potential therapeutic targets. An overview of imaging techniques that can support both research studies and clinical management is also provided. Finally, this review highlights opportunities and challenges that are necessary to advance our understanding of metabolism in the context of cardio-oncology.

Keywords: 99mTc-MIBI, 99mtechnetium-sestamibi; CVD, cardiovascular disease; D2-HG, D-2-hydroxyglutarate; FAO, fatty acid oxidation; FASN, fatty acid synthase; GLS, glutaminase; HF, heart failure; IDH, isocitrate dehydrogenase; IGF, insulin-like growth factor; MCT1, monocarboxylate transporter 1; MRS, magnetic resonance spectroscopy; PDH, pyruvate dehydrogenase; PET, positron emission tomography; PI3K, insulin-activated phosphoinositide-3-kinase; PTM, post-translational modification; SGLT2, sodium glucose co-transporter 2; TRF, time-restricted feeding; [18F]FDG, 2-deoxy-2-[fluorine-18]fluoro-D-glucose; cancer; cardio-oncology; heart failure; metabolism; oncometabolism; α-KG, α-ketoglutarate.

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Conflict of interest statement

The work was supported by the National Institutes of Health grants K99-HL-141702 (Dr Karlstaedt), R01-HL-148272 (Dr Ky), and U24-CA-220325 (Dr Gammons), Bethesda, Maryland, USA. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Metabolic Targets in HF and Cancer Key nutrients and their pathways affect how cardiomyocytes and cancer cells use metabolism to maximize ATP provision, macromolecule synthesis, redox regulation. Key reactions in central carbon metabolism shown, including the Krebs cycle, are involved in metabolic adaptation. Enzymatic targets for pharmacologic modulation are shown for reference. Created with BioRender.com. ATP = adenosine triphosphate; FFA = free fatty acids; FH = fumarate hydratase; GLS = glutaminase; HF = heart failure; IDH2 = isocitrate dehydrogenase 2; KG = ketoglutarate; PDH = pyruvate dehydrogenase; SDH = succinate dehydrogenase.
Figure 2
Figure 2
Metabolic Vulnerabilities and Use of PET Imaging Radiopharmaceuticals to study cardiac metabolic processes during disease progression and their metabolic targets are shown. Several different types of tracers have emerged that allow interrogation of metabolic pathways in patients and in vivo for pre-clinical studies. 18F-FDG = 2-deoxy-2-[fluorine-18]fluoro-D-glucose; 99mTc-MIBI = 99mtechnetium-sestamibi; ATP = adenosine triphosphate; PET = positron emission tomography. Created with BioRender.com.
Central Illustration
Central Illustration
Factors Contributing to Cardio-Oncometabolic Remodeling
See this image and copyright information in PMC

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