Translational research is a key ingredient in guiding both genetic and pharmacologic cardioprotective approaches in patients being treated for cancer, according to international experts from the International Cardio-Oncology Society and the Global Cardio-Oncology Symposium (GCOS) committee. Fadi N. Salloum, PhD, and colleagues highlighted some of the ongoing international collaborative research efforts in cardio-oncology in an article published in JACC: CardioOncology.
As stated by the investigators: “Further basic and translational research is needed to provide a better understanding of both the underlying mechanisms linking cardiovascular disease and cancer and the pathogenesis of cancer therapy–related cardiovascular toxicity and potentially actionable pathways for therapeutic discovery. Translational research on the role of genetics is required to refine cancer therapy–related cardiovascular toxicity risk-stratification scores.”
Focus of Research Efforts
One of the multinational collaborative endeavors in this arena focuses on understanding the mechanisms of cancer therapy–related cardiovascular toxicity—particularly related to the use of anthracyclines, immune checkpoint inhibitors, and Bruton’s tyrosine kinase (BTK) inhibitors—and mitigating their cardiotoxic effects. Among the topics requiring more research is elucidating the precise role of mitochondrial dysfunction and the damage many of these anticancer agents can cause to cardiac microcirculation. Other areas of interest center on the early detection of anthracycline-induced cardiotoxicity, as well as possible strategies to prevent it.
Dr. Salloum and colleagues also emphasized the importance of learning more about the role of senescence in cancer therapy–related cardiovascular toxicity, particularly in regard to doxorubicin; this agent seems to enhance heart cell senescence via DNA damage oxidative stress and mitochondrial dysfunction, they noted. In terms of immune checkpoint inhibitor–related cardiotoxicity, research efforts are turning toward CD8-positive T cells.
Another major focus of international researchers in the realm of cancer therapy–related cardiovascular toxicity is to learn more about the role of genetics and other heritable traits. “Moving forward, further development of multicenter or population-based cohorts focused on cardio-oncology variables and endpoints would enable the integration of clinical information with different -omics, such as genomics, transcriptomics, epigenomics, proteomics, and metabolomics,” the investigators noted.
Finally, although the use of immune checkpoint inhibitors has had much clinical success in treating diverse tumor types, these agents can lead to a host of immune-related adverse events, including myocarditis, atherosclerosis, and arrhythmia. Although myocarditis is relatively uncommon with these newer agents, the investigators added, it can be difficult to diagnose and there is a need for consensus on the best approach to manage patients who experience it.
Knowledge Gaps
Research priorities and gaps in knowledge regarding cardio-oncology were also flagged by the investigators. More needs to be learned about the underlying mechanisms linking cardiovascular disease and cancers as well as the pathogenesis of cancer therapy–related cardiovascular toxicity. In addition, “a comprehensive understanding of the arrhythmogenesis of cancer therapies remains incomplete and represents an area of opportunity to advance the field,” they emphasized.
The investigators concluded: “Sex-based, racial, and ethnic disparities play a key role in the overall outcomes in the field of cardio-oncology. To this end, greater efforts should be made by the scientific community to encourage and support clinical trials that improve the representation of women and racial/ethnic minorities, who unfortunately often have a higher inherent propensity to multiple comorbidities. In addition, knowledge of the impact of individual genetic predisposition on the risk of developing cancer and cancer therapy–related cardiovascular toxicity remains in its infancy for meaningful use as a risk-prediction tool.”
Dr. Salloum, of the Pauley Heart Center, Virginia Commonwealth University, Richmond, and Carlo G. Tocchetti, MD, PhD, of Federico II University, Naples, Italy, contributed equally to this work as joint first authors of the article in JACC: CardioOncology.
Disclosure: For full disclosures of the study authors, visit jacc.org.
