Molecular mechanisms involved in differentiated thyroid cancer invasion and metastasis

The majority of patients with thyroid cancer have an excellent prognosis, however patients with extensive local invasion and distant metastasis frequently do not respond to standard treatments and have worsened prognosis. Understanding the specific mechanisms involved in thyroid cancer invasion and metastasis is critical in order to develop new treatments specifically targeted for these patients.

The genetic basis for thyroid cancer initiation and development is well characterized, with the majority of studies implicating activation of the RAS-RAF-ERK and PI3K/PDK1/Akt signaling pathways. Over the last several years, data from a concerted effort to define the pathways involved in invasion and metastasis suggest that reactivation of embryonic pathways involved in cell movement, to include epithelial to mesenchymal transition and collective cell migration, may be involved in cancer cell migration and invasion. The previously identified thyroid oncogenes, BRAF, RET/PTC and Ras, appear to be important regulators of this process.

The molecular mechanisms that control cell migration during embryological development, such as epithelial to mesenchymal transition, appear to be reactivated in invading thyroid cancer cells. Elucidation of the signal-transduction networks and molecules that are involved in thyroid cancer invasion may lead to novel therapeutic targets.