Recent Advances in Methods for Circulating Tumor Cell Detection

Abstract

Circulating tumor cells (CTCs) are released from primary tumors and transported through the body via blood or lymphatic vessels before settling to form micrometastases under suitable conditions. Accordingly, several studies have identified CTCs as a negative prognostic factor for survival in many types of cancer. CTCs also reflect the current heterogeneity and genetic and biological state of tumors; so, their study can provide valuable insights into tumor progression, cell senescence, and cancer dormancy. Diverse methods with differing specificity, utility, costs, and sensitivity have been developed for isolating and characterizing CTCs. Additionally, novel techniques with the potential to overcome the limitations of existing ones are being developed. This primary literature review describes the current and emerging methods for enriching, detecting, isolating, and characterizing CTCs.

Adopted neoplastic cells and the consequences of their existence

“…This explanation is consistent with a report that only a fraction of CTC-CD45 recovered from a pancreatic cancer patient have a mutation characteristic to this cancer [52]. Given that only one of 10,000 CTC is estimated to seed a metastasis [74], adopted cells may be a candidate for this subpopulation.…”

“…Circulating tumor cells (CTC), discovered a century and a half ago [74], are neoplastic cells present in the blood of patients with solid tumors and are thought to include the precursors of metastases [75]. Paradoxically, a fraction or, in some cases, most of CTC released by some non-hematological tumors, such as melanoma, breast, ovarian, and pancreatic cancers, were found to carry CD45, a protein whose expression is normally restricted to bone-marrow derived cells [30,51,[76][77][78].…”

Advancements in Circulating Tumor Cell Research: Bridging Biology and Clinical Applications

“…As such, there is a need to refine existing techniques and develop standardized protocols while making the process cost-effective and accessible to patients [ 110 ]. Admittedly, the methodologies used to detect or isolate CTCs have evolved significantly, becoming progressively sophisticated and sensitive [ 111 , 112 , 113 , 114 ]. Current CTC detecting methods can be categorized into label-dependent (affinity-based) and label-independent [ 12 ].…”

“…Different types of PCR methods have been developed with the aim of detecting and characterizing CTCs and ctDNA [ 152 , 153 , 154 , 155 ]. These methods continue to be improved to increase sensitivity and allow for accurate and quantitative analyses of CTCs [ 111 ]. The development of droplet digital PCR (ddPCR) has allowed for the partitioning of a sample into many “droplets,” enabling the amplification of rare mutations [ 153 , 156 ].…”

Detection and Molecular Characterization of Circulating Tumour Cells: Challenges for the Clinical Setting

“…Thus, a high variety of novel ‘label-free’ CTC enrichment technologies based on CTC size and deformability have been developed [ 4 ]. These technologies can be categorized as: (i) systems based on a combination of microfluidics and size-based enrichment, such as the Parsortix system, (Angle, UK), that was FDA-cleared in May 2022 for CTC enrichment in metastatic breast cancer (MBC), (ii) filtration devices based on different CTC size, such as the ScreenCell device (Screencell, Paris, France) and the ISET system (RareCells, France), (iii) microchips with integrated nanomaterials, such as the CTC chip (NP-HBCTC-Chip) and the graphene oxide (GO) chip, (iv) systems for single CTC isolation, such as the DepArray (Menarini, Silicon Biosystems, Italy), the VyCAP (VyCAP BV, The Netherlands), and the CellCollector (ALS, Sartorius), (v) epitope-agnostic systems that detect both EpCAM-pos and EpCAM-neg CTCs, such as the EPISPOT, and the Epic platform (Epic Sciences), (vi) density-based isolation followed by antibody cocktail for imaging (RareCyte system, Rarecyte, US), and (vii) molecular tests, such as the Adnatest (Qiagen, Germany), and many others [ 1 , 2 , 3 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ].…”