Improving cardiotoxicity prediction in cancer treatment: integration of conventional circulating biomarkers and novel ex
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Improving cardiotoxicity prediction in cancer treatment: integration of conventional circulating biomarkers and novel exploratory tools Li Pang1 · Zhichao Liu2 · Feng Wei3 · Chengzhong Cai1 · Xi Yang4 Received: 13 August 2020 / Accepted: 5 November 2020 © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020
Abstract 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. Keywords Biomarkers · Clinical trials · Genetic variants · Omics · Human stem cell-derived cardiomyocytes · Artificial intelligence
Introduction
* Li Pang [email protected] 1
Division of Systems Biology, National Center for Toxicological Research, US. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA
2
Division of Bioinformation and Biostatistics, National Center for Toxicological Research, US. Food and Drug Administration, Jefferson, AR, USA
3
Department of Structural Heart Disease, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China
4
Division of Pharmacology & Toxicology, Office of Cardiology, Hematology, Endocrinology, & Nephrology, Office of New Drug, Center for Drug Evaluation and Research, US. Food and Drug Administration, Silver Spring, MD, USA
The rapid development of novel anticancer therapies has progressively made cancer a treatable chronic disease. Currently, there are around 17 million cancer survivors in the US and the number is expected to increase to more than 20 million by 2026 (NCI Cancer Statistics 2018). A surveillance study of the causes of death among 3.2 million cancer survivors in the US found that 38.0% eventually died of cancer while 11.3% died of cardiovascul
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