The Role of Circulating Tumor Cells in Diagnosis of Cancer: Cancer and Circulating Tumor Cells

An estimated 19 million new cancer cases and almost 10 million global death due to cancer in 2020 have highlighted the cardinal importance of accurate diagnostic assays for the early detection of cancer. Detecting circulating tumor cells (CTCs) offers a new approach for cancer diagnosis and treatment. Multi-disciplinary research teams have tried to develop CTC-detection assays, with the establishment of an FDA-approved test for clinical CTC enumeration and with others under development. CTC detection techniques mainly rely on physical separation and microfluidic-based methods, particularly microfiltration devices. Molecular diagnostic assays are a major group of tests used to diagnose CTCs. Among molecular diagnostic assays to detect CTCs, biochemical techniques such as immunoaffinity is a basis for enrichment involving positive and negative selection. Besides enumeration, there are multiple other techniques for CTC analysis, such as genomic, transcriptomic, epigenetic, proteomic, and multimodal analysis. However, the current CTC enumeration technology is unable to address many biological challenges associated with CTC characteristics such as extreme rarity, heterogeneous nature and varied phenotype. Future research is required for the development and application of new detection and therapeutic methods. In this review, the technical and clinical applications of the different CTCs molecular diagnostic assays are summarized, and suggestions are made to overcome caveats for CTC detection techniques in the future.