Current approaches for avoiding the limitations of circulating tumor cells detection methods—implications for diagnosis and treatment of patients with solid tumors
Introduction
Eight million people die from cancer each year1 and it is predicted that 13.2 million patients will do so in 2030.2 90% of deaths are caused by systemic disease.1 Systemic cancer spread means the formation of metastases, that is, secondary tumors arising from cells originating from the primary tumor. Thus, metastatic cancer cells are the subject of numerous studies and are an abiding interest to pharmaceutical and biotechnology companies. These cells include circulating tumor cells (CTC) in the bloodstream and disseminated tumor cells in the bone marrow. CTC are easier to analyze on a regular basis than disseminated tumor cells which require bone marrow aspiration—an invasive and painful procedure for patients with solid tumors.3
The evolution of tumor cells proceeds via multiclonal expansion which causes the tumor to be composed of multiple cell subpopulations. As a result of the accumulation of up to 6 mutations,4, 5 some cells acquire the ability to metastasize. The metastasis process consists of several sequential steps: local invasion of the primary tumor cells, intravasation, extravasation, and the establishment of distant metastasis.6 A simplified scheme of the metastatic cascade is presented in Fig 1.
https://www.translationalres.com/articl ... 8/fulltext
Current approaches for avoiding the limitations of circulating tumor cells detection methods—implications for diagnosis
The Interplay between Circulating Tumor Cells and the Immune System: From Immune Escape to Cancer Immunotherapy
The Interplay between Circulating Tumor Cells and the Immune System: From Immune Escape to Cancer Immunotherapy
Abstract
Circulating tumor cells (CTCs) have aroused increasing interest not only in mechanistic studies of metastasis, but also for translational applications, such as patient monitoring, treatment choice, and treatment change due to tumor resistance. In this review, we will assess the state of the art about the study of the interactions between CTCs and the immune system. We intend to analyze the impact that the cells of the immune system have in limiting or promoting the metastatic capability of CTCs. To this purpose, we will examine studies that correlate CTCs, immune cells, and patient prognosis, and we will also discuss relevant animal models that have contributed to the understanding of the mechanisms of immune-mediated metastasis. We will then consider some studies in which CTCs seem to play a promising role in monitoring cancer patients during immunotherapy regimens. We believe that, from an accurate and profound knowledge of the interactions between CTCs and the immune system, new immunotherapeutic strategies against cancer might emerge in the future.
Keywords: circulating tumor cells, immune system, immunotherapy, cancer biomarkers, liquid biopsy, metastasis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164896/
Abstract
Circulating tumor cells (CTCs) have aroused increasing interest not only in mechanistic studies of metastasis, but also for translational applications, such as patient monitoring, treatment choice, and treatment change due to tumor resistance. In this review, we will assess the state of the art about the study of the interactions between CTCs and the immune system. We intend to analyze the impact that the cells of the immune system have in limiting or promoting the metastatic capability of CTCs. To this purpose, we will examine studies that correlate CTCs, immune cells, and patient prognosis, and we will also discuss relevant animal models that have contributed to the understanding of the mechanisms of immune-mediated metastasis. We will then consider some studies in which CTCs seem to play a promising role in monitoring cancer patients during immunotherapy regimens. We believe that, from an accurate and profound knowledge of the interactions between CTCs and the immune system, new immunotherapeutic strategies against cancer might emerge in the future.
Keywords: circulating tumor cells, immune system, immunotherapy, cancer biomarkers, liquid biopsy, metastasis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164896/
Debbie
Re: Current approaches for avoiding the limitations of circulating tumor cells detection methods—implications for diagno
Circulating tumor cells (CTC) detection: Clinical impact and future directions
Abstract
Recent molecular and clinical studies have shown that invasion may occur very early in tumor development, thus emphasizing the potential importance of specific and sensitive detection of circulating tumor cells (CTC) and circulating tumor microemboli (CTM). The technical challenge in this field consists of finding “rare” tumor cells (just a few CTCs mixed with the approximately 10 million leukocytes and 5 billion erythrocytes in 1 ml of blood) and being able to distinguish them from epithelial non-tumor cells and leukocytes.
Many recent studies have discussed the clinical impact of detecting CTC/CTM. Although conflicting results have been obtained, these studies suggest the vast potential of CTC/CTM detection in cancer prognosis and follow up. However, the variable technical approaches which were used, as well as the number of millilitres of blood analyzed, the quality of sensitivity and specificity tests, the number of patients versus controls and the data interpretation make it very difficult to draw firm conclusions.
A particularly important recent finding is that invasive tumor cells tend to loose their epithelial antigens by the epithelial to mesenchymal transition (EMT) process. Furthermore, it is known that non-tumor epithelial cells can also be present in blood. Thus, it appears that a reliable diagnostic identification of CTC and CTM cannot be based on the expression of epithelial-specific transcripts or antigens.
Cytopathological examination of CTC/CTM, sensitively enriched from blood, represents a potentially useful alternative and can now be employed in routine analyses as a specific diagnostic assay, and be tested in large, blind, multicenter clinical trials. This basic approach can be complemented by immunological and molecular studies for further characterization of CTC/CTM and of their malignant potential.
This review is aimed at helping oncologists critically evaluate past and future research work in this field. The interest in development and assessment of this noninvasive marker should lead to more effective and better tailored anticancer treatments for individual patients, thus resulting in their improved life expectancy.
https://www.sciencedirect.com/science/a ... 3506006860
https://res.mdpi.com/d_attachment/cance ... -01930.pdf
Abstract
Recent molecular and clinical studies have shown that invasion may occur very early in tumor development, thus emphasizing the potential importance of specific and sensitive detection of circulating tumor cells (CTC) and circulating tumor microemboli (CTM). The technical challenge in this field consists of finding “rare” tumor cells (just a few CTCs mixed with the approximately 10 million leukocytes and 5 billion erythrocytes in 1 ml of blood) and being able to distinguish them from epithelial non-tumor cells and leukocytes.
Many recent studies have discussed the clinical impact of detecting CTC/CTM. Although conflicting results have been obtained, these studies suggest the vast potential of CTC/CTM detection in cancer prognosis and follow up. However, the variable technical approaches which were used, as well as the number of millilitres of blood analyzed, the quality of sensitivity and specificity tests, the number of patients versus controls and the data interpretation make it very difficult to draw firm conclusions.
A particularly important recent finding is that invasive tumor cells tend to loose their epithelial antigens by the epithelial to mesenchymal transition (EMT) process. Furthermore, it is known that non-tumor epithelial cells can also be present in blood. Thus, it appears that a reliable diagnostic identification of CTC and CTM cannot be based on the expression of epithelial-specific transcripts or antigens.
Cytopathological examination of CTC/CTM, sensitively enriched from blood, represents a potentially useful alternative and can now be employed in routine analyses as a specific diagnostic assay, and be tested in large, blind, multicenter clinical trials. This basic approach can be complemented by immunological and molecular studies for further characterization of CTC/CTM and of their malignant potential.
This review is aimed at helping oncologists critically evaluate past and future research work in this field. The interest in development and assessment of this noninvasive marker should lead to more effective and better tailored anticancer treatments for individual patients, thus resulting in their improved life expectancy.
https://www.sciencedirect.com/science/a ... 3506006860
https://res.mdpi.com/d_attachment/cance ... -01930.pdf
Debbie
Re: Current approaches for avoiding the limitations of circulating tumor cells detection methods—implications for diagno
Circulating tumour cells: their utility in cancer management and predicting outcomes
https://cureasps.org/forum/viewtopic.php?p=11956#p11956
https://cureasps.org/forum/viewtopic.php?p=11956#p11956
Last edited by D.ap on Sun Jul 18, 2021 7:29 am, edited 1 time in total.
Debbie