Circulating tumor cells (CTCs), detached from the primary tumor or metastases and shed in the patient's bloodstream, represent a relatively easily obtainable sample of the cancer tissue that can indicate the actual state of cancer, and their evaluation can be repeated many times during the course of treatment. As part of liquid biopsy, evaluation of CTCs provides a lot of clinically relevant information, which reflects the actual, real-time conditions of the disease. CTCs can be used in cancer diagnosis or screening, real-time longterm disease monitoring and even therapy guidance. Their analysis can include their number, morphology, and biological features by using immunocytochemistry and all "-omic" technologies. This review describes methods of CTC isolation and potential clinical utilization in lung cancer. Despite major advances in the diagnostics and treatment, lung cancer remains the most lethal cancer disease on a global scale. According to a WHO estimate, there were 2.09 million new lung cancer cases and 1.76 million lung cancer-related deaths in 2018 (1). Therefore, similarly to other cancer diagnoses, a significant effort is dedicated on the potential use of circulating tumor cells (CTCs) in prognosis assessment, disease monitoring and even in therapy management. CTCs, detached from the primary tumor or metastases and shed in patient's bloodstream, represent a relatively easily obtainable sample of cancer tissue. As a liquid biopsy, evaluation of CTCs provides a lot of clinically relevant information, which reflects the actual, real-time conditions of the disease (2). CTCs are very rare in the bloodstream; therefore, a number of different enrichment and isolation methods have been developed (2). Also, the evaluation of CTCs can be performed on many levels providing different kinds of information. The CTCs enrichment methods as well as their potential clinical use in lung cancer is introduced below. CTC Isolation and Detection Methods-Basic Principles Exploration of CTCs can provide a lot of clinically-relevant information; however, CTCs are very rare in the bloodstream. Every single CTC is surrounded by 10 6-10 7 mononuclear white blood cells (2, 3). Therefore, in order to be able to study and assess CTC-number and characteristics, it is necessary to separate them from the ambient blood cells. Although many methods have been developed to isolate CTCs, there are only two basic approaches to isolate CTCs: a) isolation methods based on detection of specific surface markers of the CTCs (and/or white blood cells), also called "label-dependent systems/methods" and b) methods independent of specific markers, based on physical or biological properties of the CTCs, "label-independent systems/methods" (2).
