Recent preclinical and clinical studies suggest a link between CTC clusters and worse clinical outcomes ( 3, 5). To discover better prognostic and predictive markers of early metastatic recurrence and novel targets for its prevention and treatment, it is critical to identify and characterize the CTC population with highest metastatic potential. Therefore, only the CTCs with a survival advantage during their transit in the blood stream and a better potential for colonization in the distant sites can likely contribute to metastasis. Most CTCs have a short half-life of less than 2.5 hours in circulation ( 2) and are apoptotic ( 3, 4). In fact, only a small fraction of CTCs are capable of surviving, seeding distant organs, and eventually giving rise to overt metastatic disease. Although CTCs originating from primary tumors are considered transitional in the search for a new home, most of these cells are fated to die in circulation owing to mechanical and environmental trauma such as shear forces, oxidative stress, and attack by the immune system. Solid tumors can release a surprisingly high number of circulating tumor cells (CTC) everyday into the circulation ( 1). We also offer our perspective on future directions to delineate the role of CTC clusters in metastatic cascade and discuss their clinical significance. Here, we provide insight on existing preclinical evidence on the potential mechanisms leading to CTC cluster formation and dissemination and on processes that may offer survival advantage. CTC clusters remain an underdeveloped area of research begging the attention of multidisciplinary cancer research teams. Understanding the biology of CTC clusters is critical to assess this unified scheme employed by cancer and to device strategies to overcome key pathways responsible for their improved metastatic potential. The cellular and molecular mechanisms that provide survival advantage for CTC clusters during the transit in the blood stream are also still largely unknown. However, the series of pathophysiologic events by which CTC clusters originate, enter the circulation, and reach the distant sites remain to be identified. Nor-Tech adapted Open OnDemand Plus to work with Open HPC our most prevalent Open Source cluster management suite.Circulating tumor cell (CTC) clusters may represent one of the key mechanisms initiating the metastasis process. Use NT-EZ Open OnDemand Plus instead of cryptic file editors and Linux utilities, which are not user friendly.
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