In the last decade, cardio-oncology has become a discipline on its own, with tremendous research going on to unravel the mechanisms underpinning different manifestations of cardiotoxicity caused by anticancer drugs. Although this domain is much broader than the effect of chemotherapy alone, a lot of questions about anthracycline-induced cardiotoxicity remain unknown. In this invited review, we provide insights in molecular mechanisms behind anthracycline-induced cardiotoxicity and put it in a clinical framework emphasizing the need for patients to understand, detect, and treat this detrimental condition.

Cardiovascular disease (CVD) is one of the biggest threats to public health worldwide. Identifying key genetic contributors to CVD enables clinicians to assess the most effective treatment course and prognosis, as well as potentially inform family members. This often involves either whole exome sequencing (WES) or targeted panel analysis of known pathogenic genes. In the future, tailored or personalized therapeutic strategies may be implemented, such as gene therapy. With the recent revolution in deep sequencing technologies, we know that up to 90% of the human genome is transcribed, despite only 2% of the 6 billion DNA bases coding for proteins. The long non-coding RNA (lncRNA) “genes” make up an important and significant fraction of this “dark matter” of the genome. We highlight how, despite lncRNA genes exceeding that of classical protein-coding genes by number, the “non-coding” human genome is neglected when looking for genetic components of disease. WES platforms and pathogenic gene panels still do not cover even characterized lncRNA genes that are functionally involved in the pathophysiology of CVD. We suggest that the importance of lncRNAs in disease causation and progression be taken as seriously as that of pathogenic protein variants and mutations, and that this is maybe a new area of attention for clinical geneticists.