Review of the clinical applications and technological advances of circulating tumor DNA in cancer monitoring

Yi Chang,1,2,* Bhairavi Tolani,2,* Xiuhong Nie,1 Xiuyi Zhi,3 Mu Hu,3 Biao He2 1Department of Respiratory Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China; 2Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA; 3Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China *These authors contributed equally to this work Abstract: Circulating cell-free DNA (cfDNA) released by tumor cells, termed ctDNA, closely reflects the heterogeneity of primary cancers and their metastases. As a noninvasive, real-time monitoring biomarker, ctDNA is a promising tool for detecting driver gene mutations, assessing tumor burden and acquired resistance, and early diagnosis. However, isolation and enrichment of cfDNA is a big challenge due to the high degree of DNA fragmentation and its relatively low abundance in the bloodstream. This review aims to provide insights into the recent technological advances in acquisition of optimal quality cfDNA, the use of preservatives, isolation methods, processing timelines, and detection techniques. It also describes clinical applications of ctDNA in cancer patient management. Keywords: circulating tumor DNA, ctDNA, liquid biopsy, cancer monitoring, tumor heterogeneity, targeted therapies, biomarker