Precision Cardio-Oncology

Abstract

Modern oncologic therapies and care have resulted in a growing population of cancer survivors with comorbid, chronic health conditions. As an example, many survivors have an increased risk of cardiovascular complications secondary to cardiotoxic systemic and radiation therapies. In response, the field of cardio-oncology has emerged as an integral component of oncologic patient care, committed to the early diagnosis and treatment of adverse cardiac events. However, as current clinical management of cancer therapyrelated cardiovascular disease remains limited by a lack of phenotypic data, implementation of precision medicine approaches has become a focal point for deep phenotyping strategies. In particular, -omics approaches (a field of study in biology ending in -omic, such as genomics, proteomics, or metabolomics) have shown enormous potential in identifying sensitive biomarkers of cardiovascular disease, applying sophisticated, pattern-revealing technologies to growing databases of biologic molecules. Moreover, the use of -omics to inform radiologic strategies may add a dimension to future clinical practices. In this review, we present a paradigm for a precision medicine approach to the care of cardiotoxin-exposed cancer patients. We discuss the role of current imaging techniques; demonstrate how -omics can advance our understanding of disease phenotypes; and describe how molecular imaging can be integrated to personalize surveillance and therapeutics, ultimately reducing cardiovascular morbidity and mortality in cancer patients and survivors.

The Future of Nuclear Medicine, Molecular Imaging, and Theranostics

“…The inflammatory link between heart, hematopoietic system, vessel wall, and other organs such as brain and kidneys is one timely example (26). Likewise, the recent emphasis on imaging the effects of tumors and tumor therapy on the cardiovascular system (cardio-oncology) is another example (27).…”

The Role of CYP450 Drug Metabolism in Precision Cardio-Oncology

“…Further, ontogenic changes to CYP450 activity, due to xenobiotic exposure (e.g., phenobarbital) during early development and the early postnatal period, have been shown to have long-lasting effects in mouse models. Importantly, efforts to achieve both early diagnosis and optimal treatment of disease as well as prevent and mitigate cardiac adverse effects in oncology patients has led to study and potential application of multi-omic disciplines to the field of Cardio-Oncology [7,77]. Genomics, epigenomics, transcriptomics, proteomics, miRNAomics, metabolomics and microbiomics have the potential to more precisely guide the clinical management of these patients [7,78].…”

“…Genomics, epigenomics, transcriptomics, proteomics, miRNAomics, metabolomics and microbiomics have the potential to more precisely guide the clinical management of these patients [7,78]. The integration of multi-omics with systems biology and incorporating disciplines such as mobile health (mHealth), pharmacogenomics, mathematical and computational modeling is depicted in Figures 2 and 3 and has been well described [7,77,78]. poor metabolizer phenotype and CYP2D6 metabolizes up to 20% of medications currently in use in the general population [16].…”

“…In cardioncology patients, metabolic analysis can identify a specific metabolic pattern-a metabotype-corresponding to specific (patho)physiologic states (e.g., heart failure, myocardial infarction, myocarditis, etc.) and may serve as a 'yellow-brick road,' of sorts, offering insights into the present state and potentially, the future arc of disease [7,77]. Indeed, changes in a patient's metabolic profile over time may help identify predictive biomarkers associated with different clinical trajectories, while helping to identify an individual's response to therapy (or lack thereof), preceding phenotypic changes, helping to guide therapy [7,77].…”

Emerging Challenges of Radiation-Associated Cardiovascular Dysfunction (RACVD) in Modern Radiation Oncology: Clinical Practice, Bench Investigation, and Multidisciplinary Care

“…In recent precision cardio-oncology, it is a promise direction that applies combined omic-data and metabolic-function nuclear images (117), such as single-photon emission computed tomography (SPECT) (118) and positron emission tomography (PET) (119)(120)(121)(122). Of these, PET that demonstrated metabolic changes of the heart is the most expecting image marker for detecting RACVD.…”