Detection of circulating tumor cells: Clinical relevance of a novel metastatic tumor marker

Abstract

Abstract. most cancer-related deaths are caused by the hematogenous spread of cancer cells to distant organs and their subsequent metastasis. during the early stages of the metastatic cascade, cancer cells disseminate from the primary site via the lymphatic vessels and/or by hematogenous routes. circulating tumor cells (ctcs), cancer cells that have disseminated into the systemic circulation, may be a predictor of poor prognosis in several carcinomas. an understanding of the molecular mechanisms involved in the blood-borne dissemination of cancer cells may help to clarify the process of metastasis and provide a powerful and non-invasive approach for anticancer treatments that are tailored to individual patients. Contents1. introduction 2. malignant features of metastatic ctcs 3. methods for separating ctcs 4. ctc enrichment 5. CTC identification 6. ctcs and cancer stem cells 7. clinical relevance of ctcs 8. advanced tools for tailored therapy? 9. concluding remarks 1. Introduction metastasis to distant sites (e.g., lungs, liver, bone and brain) via the bloodstream or lymph nodes is a major cause of cancer-related mortality (1-3). circulating tumor cells (ctcs) play an important role in cancer relapse and metastasis. ctcs identical to those in primary tumors were first discovered by ashworth as early as 1869 (4), and were later regarded as a hallmark of the 'leukemic phase' of cancer (5). ctcs were proposed as a novel minimally invasive prognostic and predictive marker that reflects the biological characteristics of tumors, and have been the subject of an increasing number of clinical studies. identifying cancer cells among the millions of normal blood cells during the early stages of cancer, however, is challenging. in recent years, many new methods have been developed to enrich and detect these rare ctcs in peripheral blood (6-13). the different technologies involved, coupled with the heterogeneity of the screened populations, make the clinical significance of CTCs difficult to interpret (7). thus, it is necessary to standardize the detection methods used to identify ctcs in order to determine their biological and clinical relevance. the detection of dynamic changes and malignant features within these rare cells is closely associated with the efficacy of therapy and with prognosis (6,14-24). ctcs may play an important role in the detection of early relapse and in the assessment of prognosis and the efficacy of the chosen therapy for both established cancers and metastatic precursor cells. Malignant features of metastatic CTCsOccult tumor cells may persist in a dormant or low proliferative state after curative therapy. it is these cells that are responsible for tumor relapse and metastasis. Such cells, which are not detectable by current routine diagnostic methods, may play an important role in recurrence as they may express different biological characteristics and/or markers from those of the primary tumor (25). therefore, the detection and characterization of ctcs is of the utmost clinical relevance. the proce...

Detection of apoptotic circulating tumor cells in advanced pancreatic cancer following 5-fluorouracil chemotherapy

“…It is clear that enrichment steps are necessary to increase the detection of such rare cells. 11 At present, normal and apoptotic cells were rare. 5-FU (20 μmol/L) was added to the PL45 cells and incubated for 12 and 24 h, and subsequently the number of apoptotic cells were found to be noticeably increased ( Fig.…”

Circulating tumor cells in breast cancer beyond the genotype of primary tumor for tailored therapy

“…The FDA approved The CellSearch System, and novel microfluidic chips methods are used to increase the sensitivity and specificity of the CTC detection . Malignant feature of CTCs can be validated by amplification or deletion of genes and chromosomes in different kinds of solid cancer . It may be important to include CTC measurements in TNM stage in BC to improve quality of life or increase survival by aiding decision making with respect to therapeutic strategy in the near feature.…”

“…5,100,102,103 Malignant feature of CTCs can be validated by amplification or deletion of genes and chromosomes in different kinds of solid cancer. 19,33,34,[139][140][141] It may be important to include CTC measurements in TNM stage in BC to improve quality of life or increase survival by aiding decision making with respect to therapeutic strategy in the near feature.…”

Analytical validation of the CellMax platform for early detection of cancer by enumeration of rare circulating tumor cells

“…Although CTCs have been extensively studied for more than two decades, there are few reliable methods of detecting and isolating CTCs in the early stages of cancer. [19][20][21] Experimental in vivo studies have suggested that CTCs are present early in the natural history of solid tumor growth, before the development of metastasis. 22 More recently, CTCs have been detected in the blood at early stages and at recurrence in women with breast cancer, 14,23 and in premalignant stages of prostate cancer tumor progression.…”