Forward and reverse cardio-oncology

Cardio-oncology has rapidly evolved in the past decade. It is a continuous field which was founded on the manifestation of cardiac dysfunction in patients treated with anti-cancer therapy. Short- and long-term cardiovascular compilations became known as cancer therapy-related cardiovascular toxicity (CTR-CVT). These may arise from a plethora of anti-cancer therapy, 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 healthcare professionals. This side of cardio-oncology focusses on the classical CTR-CVT side, here termed as forward cardio-oncology. On the other side is the paradigm of heart failure stimulating tumor growth, coined as reverse cardio-oncology. As cardio-oncology grew, 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.) among cardiovascular disease (CVD) and cancer grew, 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 reveal that heart failure can stimulate tumor growth in a multifaceted manner, including through a pro-tumor 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.