Review of pharmacological inhibition of thyroid cancer metabolism

Abstract

Thyroid cancer (TC) is the most common malignancy of the endocrine system and has been rapidly increasing in incidence over the past few decades. Aggressive TCs metastasize quickly and often levy poor prognoses, as they are frequently resistant to first-line treatment options. Patients diagnosed with aggressive, dedifferentiated TC have a prognosis of under a year with the most current treatment modalities. Like many cancers, TCs also exhibit altered cell metabolism, which enhances the cell’s ability to generate energy, protect against reactive oxygen species, and synthesize macromolecules such as lipids, proteins, and nucleotides for proliferation. Genetic and enzyme profiling of TC tissues and cell lines have uncovered several dysregulated metabolic pathways such as glycolysis, the pentose phosphate pathway, glutamine metabolism, and pyrimidine synthesis. These aberrations are most often due to overexpression of rate-limiting enzymes or metabolite transporters. Metabolic pathways pose attractive therapeutic targets in aggressive TC and may serve to work in tandem with standard therapeutics such as kinase inhibitors depending on the genetic, metabolic, and signaling backgrounds of individual tumors. Further studies are needed to clearly delineate altered metabolic targets across TC subtypes for implementing therapeutic metabolic inhibitors that have shown success in other aggressive tumors.