Cardiotoxicity of Antitumor Drugs; Preclinical and Clinical Readouts

Cancer therapy has witnessed impressive improvements over the last decades. New drugs became available and twisted our perception of cancer as an incurable disease. For many patients cancer can now be considered as a curable disease. For other patients chronicization of cancer is a reasonable objective to meet. Much of this progress was achieved thanks to new generation drugs that were thought to target cancer cells while also sparing the normal tissues. Thus, both cure, prolonged survival, and quality of life seemed to be at hand for growing cohorts of patients. Regrettably, however, many new drugs proved to be less “targeted” than they were considered as preclinical and clinical development landed them in the market. As patients survival increases, moderate to severe or sometime lifethreatening cardiovascular toxicity becomes apparent. Cardiotoxicity also occurs in survivors treated by old generation drugs, primarily anthracyclines. The emergence of cohorts of patients treated by old or newer cancer drugs, or by combinations of them, calls cardiologists and oncologists to devise new modalities of prevention of cardiovascular toxicity from cancer drugs. This is the clinical framework of what has become popular as Cardio-Oncology but the intellectual foundations of such new discipline actually lay on deciphering how cancer drugs cause cardiovascular events. Cardio-Oncology is in fact a pharmacologic discipline. Surveillance and treatment of patients at risk, or symptomatic for cardiotoxicity is only possible if pharmacologic insight is at hand.

In spite of the steadily growing number of "cardio-oncology” publications, molecular mechanisms and clinical correlates of cancer drugs cardiovascular toxicity remain a black box. For the venerable anthracyclines, no single mechanistic hypothesis can really be said to embrace the whole spectrum of preclinical and clinical findings. For the newer drugs, some evidence suggests that cardiovascular toxicity can be both “on” and “off” target but one-to-one translation in clinical facts is lacking for the vast majority of cases. On the other hand, some pitfalls of drug development need to be put in a context, such that what is often referred to as “unexpected” cardiovascular toxicity from a given drug is in fact the overlap of unknown molecular mechanisms and predictable consequences of herratic drug testing. Pathophysiologic interactions between “potential” toxicity from a given drug and individual predisposition, whether caused by genetic factors or comorbidities, also merit an adequate consideration.

This Research Topic aims at intercepting and discussing a number of cardio-oncology issues, in the hope of providing the expert, and the non expert as well, with a scholar summary of what is known, uncertain, or definitely unknown in this field. Much attention is obviously paid to the pharmacologic foundations of cancer drugs toxicity but an equal consideration is given to translating molecular facts into clinical notions.