Prognostic and Therapeutic Role of Angiogenic Microenvironment in Thyroid Cancer

Abstract

Thyroid cancer is the most common endocrine malignancy, with a typically favorable prognosis following standard treatments, such as surgical resection and radioiodine therapy. A subset of thyroid cancers progress to refractory/metastatic disease. Understanding how the tumor microenvironment is transformed into an angiogenic microenvironment has a role of primary importance in the aggressive behavior of these neoplasms. During tumor growth and progression, angiogenesis represents a deregulated biological process, and the angiogenic switch, characterized by the formation of new vessels, induces tumor cell proliferation, local invasion, and hematogenous metastases. This evidence has propelled the scientific community's effort to study a number of molecular pathways (proliferation, cell cycle control, and angiogenic processes), identifying mediators that may represent viable targets for new anticancer treatments. Herein, we sought to review angiogenesis in thyroid cancer and the potential role of proangiogenic cytokines for risk stratification of patients. We also present the current status of treatment of advanced differentiated, medullary, and poorly differentiated thyroid cancers with multiple tyrosine kinase inhibitors, based on the rationale of angiogenesis as a potential therapeutic target.

Keywords: angiogenesis process; angiogenic microenvironment; antiangiogenic therapy; cell cycle control pathways; prognostic factors; proliferation pathways; therapeutic target; thyroid carcinoma; tumor behavior; tumor microenvironment.

Figure 1

The angiogenic microenvironment of thyroid cancer: interactions between cancer cells, stromal cells, and inflammatory cells to promote angiogenesis and tumor progression.