Targeting lipid metabolism for the treatment of anaplastic thyroid carcinoma

Abstract

Introduction: Anaplastic thyroid carcinoma (ATC) is the rarest subtype of thyroid cancer; however, it disproportionately accounts for a large percentage of all thyroid cancer-related deaths and is considered one of the most lethal solid tumors in humans, having a median survival of only a few months upon diagnosis. Although a variety of treatment options are available including surgery, radiation and targeted therapies, response rates are low, due in part to the drug-resistant nature of this disease; therefore, new avenues for therapeutic intervention are surely needed. Recent investigation into the metabolic profile of ATC has revealed a tumor-specific dependency for increased de novo lipogenesis, offering new insight into the molecular mechanisms that govern disease initiation and progression.

Areas covered: Herein we summarize known oncogenic signaling pathways and current therapeutic strategies for the treatment of ATC. We further discuss the unique expression pattern of lipid metabolism constituents in this disease. Additionally, the current literature correlating aberrant lipogenesis with carcinogenesis is reviewed, and the implications of targeting this pathway as an innovative approach for treating ATC and other malignancies are discussed. As stearoyl-CoA desaturase (SCD) is the most differentially expressed constituent of lipid metabolism in ATC, an additional focus on this enzyme as a novel therapeutic target is applied.

Expert opinion: This section is used to summarize the current research efforts underway in defining the role of lipid metabolism specifically in thyroid carcinoma. Included is a brief summary of lipid metabolism factors for which inhibitors have been generated and are under current investigation as anti-cancer agents. Finally, research limitations regarding the use of these inhibitors against components of this pathway are discussed.

Keywords:

• anaplastic thyroid carcinoma
• carcinogenesis
• chemoresistance
• de novo lipogenesis
• fatty acid synthase
• fatty acids
• lipid metabolism
• stearoyl-CoA desaturase
• sterol regulatory-element binding protein

Declaration of interest

CA von Roemeling and JA Copland were supported by the National Cancer Institute (NCI) of the National Institutes of Health (NIH) under award number R01CA136665; the Florida Department of Health under Bankhead-Coley Cancer Research Program grant number FL09B202. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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