Metastatic mechanisms in follicular cell-derived thyroid cancer

Abstract

Thyroid cancer incidence is rising annually largely related to enhanced detection and of early stage well-differentiated primary tumors. The prognosis for patients with early stage thyroid cancer is outstanding with most patients being cured with surgery. In selected cases, I-131 is administered to treat known or suspected residual or metastatic disease. Even patients with loco-regional metastases typically have an outstanding long-term prognosis, albeit with monitoring and occasional intervention for residual or recurrent disease. In contrast, individuals with distant metastases from thyroid cancer, particular older patients with larger metastatic burdens and those with poorly differentiated tumors, have a poor prognosis. Patients with metastatic anaplastic thyroid cancer have a particularly poor prognosis. Published clinical trials indicate that transient disease control and partial remissions can be achieved with kinase inhibitor therapy directed toward angiogenic targets, and that in some cases, I-131 uptake can be enhanced. However, the direct targets of activity in metastatic lesions are incompletely defined and clear evidence that these treatments increase the duration or quality of life of patients is lacking, underscoring the need for improved knowledge regarding the metastatic process to inform the development of new therapies. In this review, we will focus on current data and hypotheses regarding key regulators of metastatic dormancy, metastatic progression, and the role of putative cancer stem cells.

Cancer stem-like cells and thyroid cancer

“…Vimentin overexpression was associated with invasion and nodal metastases (Vasko et al 2007, Phay & Ringel 2013. Hardy et al (2007) examined the Snail family of transcription factors and reported that these were associated with thyroid carcinogenesis.…”

“…As a great deal of research on EMT is to inhibit cancer cells in the mesenchymal state, these approaches may have stimulatory effects on established metastases or even activate dormant cancer cells. The concept of metastatic dormancy during the metastatic cascade is an important feature of metastatic disease (Phay & Ringel 2013). Metastatic dormancy may include physical barriers provided by extracellular matrices, as well as expression of proteins encoded by metastatic suppressor genes (Phay & Ringel 2013).…”

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

“…However, such approaches may have stimulatory effects on existing metastatic foci or may even activate dormant cancer cells. 41,42 The concept of metastatic dormancy during the metastatic cascade is an important feature of metastatic disease. 41 Metastatic dormancy may include physical barriers provided by extracellular matrices or protein expression encoded by suppressor genes.…”

“…41,42 The concept of metastatic dormancy during the metastatic cascade is an important feature of metastatic disease. 41 Metastatic dormancy may include physical barriers provided by extracellular matrices or protein expression encoded by suppressor genes. The goals of understanding the biology of EMT and MET should include designing better drugs to target cancer cells including CSCs more effectively.…”

“…The goals of understanding the biology of EMT and MET should include designing better drugs to target cancer cells including CSCs more effectively. 41,42 SIGNALING PATHWAYS IN CSCs Specific signaling pathways have been described in embryonic stem cells and more recently in CSCs. These pathways are critical in the regulation of self-renewal and survival for both stem cells and CSCs.…”