Biomarkers for safety and toxicology: Drug induced cardiac injury and dysfunction

Cancer chemotherapeutic drugs, by their very nature of targeting robust and often rapidly dividing cells, inherently carry more toxicological burden and risk than drugs aimed at treating more benign disease. However, clinical oncologists have a continual need to utilise every therapeutic tool in their armoury in their attempts to treat this debilitating and often fatal disease. It is important that the physician has suitable biomarkers not only for efficacy, but also for drug related toxicity, in order to exploit maximally what is often a narrow therapeutic margin between benefit and unacceptable toxicity. Here we present data on a novel anticancer agent intended for combination therapy. The drug caused impaired cardiac functionality in pre- clinical studies at high doses, potentially leading to restrictive exclusion criteria in early clinical trials. To assist in clinical development, we generated biomarker data to be used in a weight of evidence approach to increase confidence in safe clinical progression.