Circulating tumour cells: their utility in cancer management and predicting outcomes

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Circulating tumour cells: their utility in cancer management and predicting outcomes


“Abstract
Recent advances in technology now permit robust and reproducible detection of circulating tumour cells (CTCs) from a simple blood test. Standardization in methodology has been instrumental in facilitating multicentre trials with the purpose of evaluating the clinical utility of CTCs. We review the current body of evidence supporting the prognostic value of CTC enumeration in breast, prostate and colorectal cancer, using standardized approaches, and studies evaluating the correlation of CTC number with radiological outcome. The exploitation of CTCs in cancer management, however, is now extending beyond prognostication. As technologies emerge to characterize CTCs at the molecular level, biological information can be obtained in real time, with the promise of serving as a ‘surrogate tumour biopsy’. Current studies illuminate the potential of CTCs as pharmacodynamic and predictive biomarkers and potentially their use in revealing drug resistance in real time. Approaches for CTC characterization are summarized and the potential of CTCs in cancer patient management exemplified via the detection of epidermal growth factor receptor mutations from CTCs in patients with non-small cell lung cancer. The opportunity to learn more about the biology of metastasis through CTC analysis is now being realized with the horizon of CTC-guided development of novel anticancer therapies.“

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126032/

The challenges of Detecting circulating tumor cellls (CTC),in sarcomas

https://www.frontiersin.org/articles/10 ... .00202/pdf

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“Circulating tumor cells (CTCs) are associated with abnormalities in peripheral blood dendritic cells in patients with inflammatory breast cancer”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482606/

“Dendritic cells (DCs) are the most efficient antigen presenting cells and are comprised of plasmacytoid-(pDC) and myeloid-(mDC) derived DC subsets. This study aimed to correlate CTC counts with the peripheral blood DC immunophenotypes and functions of inflammatory breast cancer (IBC) patients”

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“The rearrangement results in the expression of chimeric transcripts, which can be identified by means of reverse transcriptase–polymerase chain reaction (RT-PCR). We investigated …”

https://scholar.google.com/scholar?q=ci ... Le6JK6SksJ


RT-PCR suggests human skeletal muscle origin of alveolar soft-part sarcoma.

https://www.ncbi.nlm.nih.gov/m/pubmed/10838498/

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Abstract
Sarcomas are a heterogeneous group of malignant neoplasms of mesenchymal origin, many of which have a propensity to develop distant metastases. Cancer cells that have escaped from the primary tumor are able to invade into surrounding tissues, to intravasate into the bloodstream to become circulating tumor cells (CTCs), and are responsible for the generation of distant metastases. Due to the rarity of these tumors and the absence of specific markers expressed by sarcoma tumor cells, the characterization of sarcoma CTCs has to date been relatively limited. Current techniques for isolating sarcoma CTCs are based on size criteria, the identification of circulating cells that express either common mesenchymal markers, sarcoma-specific markers, such as CD99, CD81, or PAX3, and chromosomal translocations found in certain sarcoma subtypes, such as EWS-FLI1 in Ewing’s sarcoma, detection of osteoblast-related genes, or measurement of the activity of specific metabolic enzymes. Further studies are needed to improve the isolation and characterization of sarcoma CTCs, to demonstrate their clinical significance as predictive and/or prognostic biomarkers, and to utilize CTCs as a tool for investigating the metastatic process in sarcoma and to identify novel therapeutic targets. The present review provides a short overview of the most recent literature on CTCs in sarcoma.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013264/

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Size Matters for Sarcomas!



Abstract
INTRODUCTION
By the time of diagnosis, sarcomas have frequently reached a large size and many patients have a long history of symptoms prior to diagnosis. The aim of this study was to assess whether size of tumour at presentation or duration of symptoms was a significant factor affecting outcome.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1963770/

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The Challenges of Detecting Circulating Tumor Cells in Sarcoma


http://www.cureasps.org/forum/viewtopic ... 962#p11957

Introduction
Sarcomas are a heterogeneous group of soft tissue and bone neoplasms that arise from mesoderm or ectoderm (1) and consequently may arise from mesenchymal stem cells (2). Helman and Meltzer (3) associated different molecular alterations with specific histological entities and suggested that sarcomas can be defined by their molecular signatures. This observation is strengthened by recent publications identifying a specific subgroup of thoracic sarcomas based on SMARC4A inactivation (4) and a “BRCA-ness” signature in osteosarcomas (5). These molecular signatures include sarcoma-specific translocations that result in oncogenic fusion genes, which are believed to be necessary for malignant transformation and are utilized for molecular-based subgrouping.

Distant metastases develop in half of sarcoma patients presenting initially with localized disease, with the lungs being the most common metastatic site (1). The vast majority of sarcomas, excepted epithelioid sarcoma, angiosarcoma, and alveolar rhabdomyosarcoma, which can invade regional lymph nodes, predominantly spread through the blood vasculature. This modality is not exclusive and can be associated with spread from the lymphatic system into the blood vasculature (6). To generate metastases, tumor cells must overcome several constraints: escape from the primary site through the invasion of cancer cells from the basal membrane into a blood or lymphatic vessel, a process called intravasation (7); survival in the circulation; arrest in the capillaries at a new site; migration from the capillary into the interstitial space; and establishment of tumor growth at the new location (Figure ​(Figure1).1). As these steps are sequential and dependent on each other, only a small number of cells will successfully complete all of them, illustrating the considerable inefficiency of the metastatic process (8). Interestingly, communications between tumor cells and the host tissue play an important role in the establishment and development of metastatic foci (9–11).

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Current methods to detect tumor recurrence or the development of metastasis is largely dependent on clinical examination and/or radiographic imaging to identify the location/expansion of tumor growth, such as computerized tomography (CT), which uses multiple X-rays to produce cross-sectional layers that show detailed images inside the body, including bones, organs, tissues, and tumors (12), or positron emission tomography based on the injection, inhalation, or swallowing of radioactive tracers. Metabolic disturbances associated with tumor growth can be then detected by these techniques (13). These approaches present some advantages: (i) they are painless, easy to set up, and rapid; (ii) they can help in the diagnosis and serve as a guide for treatment; (iii) they can be used in the treatment follow-up. Nevertheless, these methodologies show also important disadvantages such as (i) exposure to ionizing radiation (X-ray or gamma rays) with potential risks of secondary cancer; (ii) injection of a contrast medium (dye) can cause kidney problems or result in allergic/injection-site reactions in some patients; and (iii) some procedures require anesthesia (14–16). New methods are needed to enable the earlier detection of tumor recurrence and metastasis, and to improve the diagnosis, treatment, and surveillance of patients suffering from sarcoma. Detection of circulating tumor cells (CTCs), as a measure of metastatic potential, could provide a way to target a patient population more likely to benefit from adjuvant chemotherapy. To date, however, the clinical significance of CTCs, as a prognostic or predictive marker in sarcoma, is uncertain.

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Circulating tumor cells can be detected in the peripheral blood and in theory have the potential to extravasate to form tumor metastases (17). CTCs are cells that circulate in the peripheral blood, while disseminated tumor cells (DTCs) are cells located in secondary organs such as bone marrow. DTCs then derive from CTCs. Interestingly, Kim et al. (18) suggested that DTCs converted into CTCs can also return to and enrich the primary tumor, a process termed “tumor self-seeding” or “cross-seeding.”

http://www.cureasps.org/forum/viewtopic ... 546#p11839