Angiogenesis as a Treatment Avenue for Anaplastic Thyroid Carcinoma

Edward Parker Whitfield

Introduction: Anaplastic thyroid carcinoma (ATC) arises in the follicular cells of the thyroid gland5. Unlike the 90% of follicular carcinomas that are well differentiated, ATC exhibits a high level of dedifferentiation, local aggression, metastasis, and fatality5,6. ATC has distant metastases in 50% of patients at the time of diagnosis, and rapid local progression leading to suffocation is the most common cause of death5.  ATC accounts for 1-2% of all thyroid cancers with 1-2 cases per million per year in the US, and has a median survival time of 5-6 months with only 10-15% of patients surviving 2 years after presentation5.  The ineffectiveness of current treatments including, chemotherapy, radiation, and surgery has led to pursuit of novel therapies including the inhibition of tumor angiogenesis5. Some potential avenues for angiogenesis inhibition in ATC are the drugs apatanib and CLM3, and the oncolytic virus dl922-9471,3,8. Methods: A combination of in vitro human ATC cell line experiments and nude mice ATC tumor model experiments were run to investigate these treatment options. Results: Apatanib decreased angiogenic proteins ANG (angiogenin) and VEGFR2 (vascular endothelial growth factor receptor) in human ATC cells in vitro3. CLM3 was shown to decrease activation of ERK1/2 (extracellular regulated kinase) pathways in vitro, which inhibits endothelial cell proliferation1 . CLM3 was also shown to decrease VEGF and tumor microvessel density in vivo in mice growing human ATC tumors1. Adenovirus dl922-947 was shown to decrease Interleukin 8 (a promoter of cellular proliferation and migration) levels, and tumor microvessel density in vivo in mice growing human ATC tumors8. Conclusion: The metastatic and local aggressiveness of ATC are dependent on tumor neovascularization to supply nutrients for growth. This makes angiogenesis a good target for new therapies. In light of the evidence that the above treatment methods did significantly inhibit angiogenesis in ATC cell lines and tumors it is possible that these treatments will be able to improve the decidedly poor prognosis that currently comes with ATC.

 

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