Circulating tumor cell
Circulating tumor cells (CTCs) are cells that have shed into the vasculature from a primary tumor and circulate in the bloodstream. CTCs thus constitute seeds for subsequent growth of additional tumors (metastasis) in vital distant organs, triggering a mechanism that is responsible for the vast majority of cancer-related deaths.CTCs were observed for the first time in 1869 in the blood of a man with metastatic cancer by Thomas Ashworth, who postulated that “cells identical with those of the cancer itself being seen in the blood may tend to throw some light upon the mode of origin of multiple tumours existing in the same person”. A thorough comparison of the morphology of the circulating cells to tumor cells from different lesions led Ashworth to conclude that “One thing is certain, that if they [CTC] came from an existing cancer structure, they must have passed through the greater part of the circulatory system to have arrived at the internal saphena vein of the sound leg”.The importance of CTC's in modern cancer research began in the mid 1990's with the demonstration [J. Uhr, UT-Dallas, L. Terstappen and P. Liberti, Immunicon, Philadelphia] that CTC's exist early on in the course of the disease. Those results were made possible by exquisitely sensitive magnetic separation technology employing Ferrofluids (colloidal magnetic nanoparticles) and high gradient magnetic separators invented by Liberti at Immunicon and motivated by theoretical calculations by Liberti and Terstappen that indicated very small tumors shedding cells at less than 1.0 % per day should result in detectable cells in blood. A variety of other technologies have been applied to CTC enumeration and identification since that time.Modern cancer research has demonstrated that CTCs derive from clones in the primary tumor, validating Ashworth's remarks. The significant efforts put into understanding the CTCs biological properties have demonstrated the critical role circulating tumor cells play in the metastatic spread of carcinoma.Furthermore, highly sensitive, single-cell analysis demonstrated a high level of heterogeneity seen at the single cell level for both protein expression and protein localization and the CTCs reflected both the primary biopsy and the changes seen in the metastatic sites. Tissue biopsies are poor diagnostic procedures: they are invasive, cannot be used repeatedly, and are ineffective in understanding metastatic risk, disease progression, and treatment effectiveness. CTCs thus could be considered a “liquid biopsy” which reveals metastasis in action, providing live information about the patient’s disease status. Analysis of blood samples found a propensity for increased CTC detection as the disease progressed in individual patients. Blood tests are easy and safe to perform and multiple samples can be taken over time. By contrast, analysis of solid tumors necessitates invasive procedures that might limit patient compliance. The ability to monitor disease progression over time could facilitate appropriate modification to a patient's therapy, potentially improving their prognosis and quality of life.To this end, technologies with the requisite sensitivity and reproducibility to detect CTCs in patients with metastatic disease have recently been developed.