The importance of early cancer diagnosis and improved cancer therapy has been clear
for years and has initiated worldwide research towards new possibilities in the care
strategy of patients with cancer using technological innovations. One of the key research
fields involves the separation and detection of circulating tumor cells (CTC) because
of their suggested important role in early cancer diagnosis and prognosis, namely,
providing easy access by a liquid biopsy from blood to identify metastatic cells before
clinically detectable metastasis occurs and to study the molecular and genetic profile
of these metastatic cells. Provided the opportunity to further progress the development
of technology for treating cancer, several CTC technologies have been proposed in
recent years by various research groups and companies. Despite their potential role
in cancer healthcare, CTC methods are currently mainly used for research purposes,
and only a few methods have been accepted for clinical application because of the
difficulties caused by CTC heterogeneity, CTC separation from the blood, and a lack
of thorough clinical validation. Therefore, the standardization and clinical application
of various developed CTC technologies remain important subsequent necessary steps.
Because of their suggested future clinical benefits, we focus on describing technologies
using whole blood samples without any pretreatment and discuss their advantages, use,
and significance. Technologies using whole blood samples utilize size-based, immunoaffinity-based,
and density-based methods or combinations of these methods as well as positive and
negative enrichment during separation. Although current CTC technologies have not
been truly implemented yet, they possess high potential as future clinical diagnostic
techniques for the individualized therapy of patients with cancer. Thus, a detailed
discussion of the clinical suitability of these new advanced technologies could help
prepare clinicians for the future and can be a foundation for technologies that would
be used to eliminate CTCs in vivo.