Editorial: Cardio-oncology and reverse cardio-oncology: the manifold interconnections between heart failure and cancer

Conversely, growing evidence suggests a role of germline genetic variants in mediating the risk of CTRC and the possibility of leveraging these variants to identify patients at risk for CTRC and to guide treatment decisions as well as monitoring and management strategies. In this respect, Yang et al. performed a meta-analysis of 41 studies investigating the relationship between genetic variations and CTRC, with a primary focus on anthracycline-based and HER2-targeted therapies. Out of 14 single nucleotide polymorphisms that were consistently detected in the 41 studies, 6 variants were strongly associated with the increased risk for CTRC. Of note, these variants were anticipated to affect the activity of drug transporters, thus being responsible for drug accumulation and/or excessive reactive oxygen species generation, leading to exaggerated cardiotoxicity. Nevertheless, the pathogenic and mechanistic roles of these variants in mediating cardiotoxicity warrant further investigations.While acknowledging the importance of CV toxicity of anticancer therapies, contemporary cardiooncology has widened its focus, since mounting evidence indicates that CVD and cancer are linked to one another at multiple levels [3]. The nascent field of reverse cardio-oncology has started to reveal the biological processes shared by cancer and heart failure (HF), such as chronic systemic inflammation and clonal hematopoiesis of indeterminate potential [4]. Shared risk factors, such as obesity, also contribute to the interconnection between CVD and HF and represent actionable therapeutic targets. In this Research Topic, Guha et al. highlighted a further layer of complexity in the interplay between risk factors, CVD, and cancer, proposing socioeconomic disparity and ancestry as mediators of obesity-driven higher predisposition to CVD and cancer in African Americans (AA) compared to Caucasians. On the one hand, socio-economic disparity hinders access to a healthy lifestyle among AA while, on the other hand, polymorphisms of two genes, APOL1 and ACKR1, were found more frequent in AA than in other ethnicities, suggesting the existence of genetic determinants. Although ACKR1 is a strong attractant of monocytes and could account for enhanced monocyte mobilization and activation in AA, further studies are required to clarify its clinical relevance.Another cellular process strictly intertwined with inflammation and that could underlie the occurrence of both cancer and CVD is senescence. The review article by Banerjee et al. discussed how the conventional concept of senescence as the mediator of cell cycle arrest has been progressively replaced by the view according to which senescent cells can remain metabolically active and secrete pro-inflammatory mediators known as senescence-associated secretory phenotype (SASP). The article provided an overview of recent evidence suggesting that SASP can be at the intersection of CVD and cancer, suggesting the use of senolytics as an approach for the treatment of both diseases.Irrespective of common underlying pathways, the interrelation between CVD and cancer is confirmed by the prognostic value that biomarkers classically associated with one condition also play in the other one. While it was previously shown that increased concentrations of established markers of CVD portend a higher risk of cancer incidence and mortality [5], Bracun et al. now reported that 6 tumor biomarkers also predicted CVD and CV mortality in more than 8,000 subjects enrolled in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study, which was originally conducted to assess renal disease and CVD in a large cohort sample in The Netherlands. The strongest associations were for CEA and CYFRA 21-1 and, interestingly, differences were observed between males and females, which are worth of additional investigation.In conclusion, this Research Topic highlights that CVD and cancer are interlinked by shared genetic and non-genetic risk factors, and common mechanistic basis, like inflammation and senescence. Interestingly, anticancer therapies may exacerbate CVD in cancer patients by impinging on the same molecular processes, which could thus represent actionable targets to prevent CTRC.