Future of circulating tumor cells in the melanoma clinical and research laboratory settings.
Circulating tumor cells (CTC) have become a field of interest for oncologists based on the premise that they constitute the underpinning for metastatic dissemination. The lethal nature of cancer is no longer attributed to solid tumor formation, but rather to the process of metastasis; shifting the focus of current studies towards the isolation and identification of metastatic progenitors, such as CTCs. CTCs originate from primary tumor masses that undergo morphologic and genetic alterations, which involve the release of mesenchymal-like cancer cells into the bloodstream, capable of invading nearby tissues for secondary tumor development. Cancerous cells contained in the primary tumor mass acquire the motile mesenchymal phenotype as a result of the Epithelial-to-Mesenchymal Transition, where substantial variations in protein expression and signaling pathways take place. CTCs that migrate from the primary tumor, intravasate into the systemic vasculature, are transported through the bloodstream, and invade tissues and organs suitable for secondary tumor development. While only a limited number of CTCs are viable in the bloodstream, their ability to elude the immune system, evade apoptosis and successfully metastasize at secondary tumor sites, makes CTCs promising candidates for unraveling the triggers that initiates the metastatic process. In this article, these subjects are explored in greater depth to elucidate the potential use of CTCs in the detection, disease staging and management of metastatic melanoma.
The Pennsylvania State University College of Medicine, Departments of Pharmacology, 500 University Drive, Hershey, PA 17033, USA. Electronic address: ldesouza@pennstatehealth.psu.edu.
Luisa M
LM
De Souza
The Pennsylvania State University College of Medicine, Departments of Pharmacology, 500 University Drive, Hershey, PA 17033, USA.
Bailey M
BM
Robertson
The Pennsylvania State University College of Medicine, Departments of Pharmacology, 500 University Drive, Hershey, PA 17033, USA; Pathology, 500 University Drive, Hershey, PA 17033, USA; Dermatology, 500 University Drive, Hershey, PA 17033, USA; Surgery, 500 University Drive, Hershey, PA 17033, USA; The Melanoma and Skin Cancer Center, 500 University Drive, Hershey, PA 17033, USA; The Melanoma Therapeutics Program, 500 University Drive, Hershey, PA 17033, USA. Electronic address: gprobertson@psu.edu.
Gavin P
GP
Robertson
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D002465:Cell Movement; D002469:Cell Separation / Q000379:methods; D002470:Cell Survival; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008545:Melanoma / Q000097:blood / Q000235:genetics / Q000556:secondary* / Q000628:therapy; D009361:Neoplasm Invasiveness; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012878:Skin Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology* / Q000628:therapy
D014408:Biomarkers, Tumor
Circulating melanoma cells; Heterogeneity; Personalized therapy