Forward and reverse cardio-oncology

Cardio-oncology has rapidly evolved in the past decade. It is a continuous field that was founded on the manifestation of cardiac dysfunction in patients treated with anticancer therapy. Short- and long-term cardiovascular complications became known as cancer therapy-related cardiovascular toxicity (CTR-CVT). These may arise from a plethora of anticancer therapies, including broad classes such as chemotherapy, immunotherapy, and hormonal therapy. Recently, the first European Society of Cardiology guideline on cardio-oncology was published, providing expert consensus on definitions, diagnosis, treatment, and prevention for health-care professionals. This side of cardio-oncology focuses on the classical CTR-CVT, here termed forward cardio-oncology. On the other side is the paradigm of heart failure stimulating tumor growth, coined as reverse cardio-oncology. As cardio-oncology expanded, the knowledge of co-occurrence of these disease entities in the same individuals grew. This raised the question of whether this phenomenon was due to shared risk factors (i.e. diabetes mellitus, obesity, etc.) between cardiovascular disease (CVD) and cancer or because of shared underlying mechanisms, and thus whether the presence of one of the two disease entities could drive the onset or progression of the other. Indeed, mechanistic studies revealed that heart failure can stimulate tumor growth in a multifaceted manner, including through a protumor cardiac secretome, by immune system modulation, or even through the gut microbiome. This review provides an extensive and robust overview of the current knowledge on the entirety of cardio-oncology and highlights future perspectives for research.