Future of circulating tumor cells in the melanoma clinical and research laboratory settings

Publication date: 28 April 2017
Source:Cancer Letters, Volume 392
Author(s): Luisa M. De Souza, Bailey M. Robertson, Gavin P. Robertson
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.

Teaser

Significance: The clinical promise of CTCs to serve as a predictive tool of assessment for disease staging, drug efficacy, personalization of therapeutic agents, disease-free-duration, and overall patient survival, is limited by CTC isolation technology, CTC heterogeneity, and a need for a better understanding of CTC biology. However, the CTC field can still provide valuable insight into tumor depiction, metastatic pathway elucidation, as well as the determination of precise diagnostic and prognostic tools in disease-free survival.


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