Improving cardiotoxicity prediction in cancer treatment: integration of conventional circulating biomarkers and novel exploratory tools

Early detection strategies and improvements in cancer treatment have dramatically reduced the cancer mortality rate in the United States (US). However, cardiovascular (CV) side effects of cancer therapy are frequent among the 17 million cancer survivors in the US today, and cardiovascular disease (CVD) has become the second leading cause of morbidity and mortality among cancer survivors. Circulating biomarkers are ideal for detecting and monitoring CV side effects of cancer therapy. Here, we summarize the current state of clinical studies on conventional serum and plasma CVD biomarkers to detect and prevent cardiac injury during cancer treatment. We also review how novel exploratory tools such as genetic testing, human stem cell-derived cardiomyocytes, Omics technologies, and artificial intelligence can elucidate underlying molecular and genetic mechanisms of CV injury and to improve predicting cancer therapy-related cardiotoxicity (CTRC). Current regulatory requirements for biomarker qualifications are also addressed. We present generally applicable lessons learned from published studies, particularly on how to improve reproducibility. The combination of conventional circulating biomarkers and novel exploratory tools will pave the way for precision medicine and improve the clinical practice of prediction, detection, and management of CTRC.