Circulating Tumor Cells: Fluid Surrogates of Solid Tumors

Abstract

Evaluation of circulating tumor cells (CTCs) has demonstrated clinical validity as a prognostic tool based on enumeration, but since the introduction of this tool to the clinic in 2004, further clinical utility and widespread adoption have been limited. However, immense efforts have been undertaken to further the understanding of the mechanisms behind the biology and kinetics of these rare cells, and progress continues toward better applicability in the clinic. This review describes recent advances within the field, with a particular focus on understanding the biological significance of CTCs, and summarizes emerging methods for identifying, isolating, and interrogating the cells that may provide technical advantages allowing for the discovery of more specific clinical applications. Included is an atlas of high-definition images of CTCs from various cancer types, including uncommon CTCs captured only by broadly inclusive nonenrichment techniques.

Emerging Role of Circulating Tumor Cells in Gastric Cancer

“…Once CTCs enter the bloodstream, they have the potential to colonize to the distant organs and establish metastases or return to their primary tumor site(s). However, even with the extensive modifications they have undergone, most CTCs, whether they are circulating individually or in clusters, are unable to survive in the hostile environment of the vasculature before they can extravasate into surrounding tissues [13].…”

“…Therefore, the use of CTCs for cancer screenings is really promising, as the routine profiling and detection of CTCs from the blood could lead towards the development of a far more efficient, noninvasive system for detection of tumors. Additionally, CTCs exhibit certain properties and unique molecular traits of the primary tumor that could provide valuable insights into possible mechanisms of cancer treatment [12][13][14].…”

Challenges and unanswered questions for the next decade of circulating tumour cell research in lung cancer

“…More recently, imaging and scanning technologies have been developed to a point where CTCs can be visualised, identified and isolated without any prior enrichment (8). A number of integrated systems have been described for the interrogation of whole blood including high definition single cell analysis (HD-SCA) (29) and the RareCyte system (RareCyte, Seattle, WA, USA) (30) ( Table 1).…”

“…A number of integrated systems have been described for the interrogation of whole blood including high definition single cell analysis (HD-SCA) (29) and the RareCyte system (RareCyte, Seattle, WA, USA) (30) ( Table 1). Both are based on the principle of "no cell left behind" where all nucleated blood cells are deposited on microscope slides and stained with markers allowing discrimination of blood and nonblood cells thereby increasing the possibility to detect rare CTCs subpopulations (8). An additional feature for both the HD-SCA and RareCyte ® platforms is that, once candidate…”

“…We will reference CTC studies across all cancer types but will highlight studies addressing lung cancer CTCs. Given the broad scope of CTC research and the large numbers of CTC publications we cannot provide an exhaustive coverage of the subject so for those requiring more detail we would recommend recent excellent CTC reviews (7)(8)(9).…”