Endocrine Abstracts

Background: The sodium/iodide symporter (NIS) frequently shows diminished targeting to the plasma membrane (PM) in differentiated thyroid cancer, resulting in suboptimal radioiodine treatment and poor prognosis. However, the mechanisms which govern the endocytosis of NIS away from the PM – its sole site of transport activity – are ill-defined, and may be of direct therapeutic potential. We previously showed that the proto-oncogene PBF binds NIS and enhances its inter...

Introduction: Radioactive iodine (RAI) therapy is a critical component in the post-surgical management of thyroid cancer patients, as well as being a central therapeutic option in the treatment of hyperthyroidism. Previous work suggests that antithyroid drugs hinder the efficacy of RAI therapy in patients. However, the effects of other background medications on RAI treatment efficacy have not been evaluated. Therefore, we performed a systematic review and metanalysis investiga...

Introduction: New drug approaches are urgently required to improve radioiodide (RAI) uptake for efficient ablation of thyroid cancer cells in RAI-refractory disease. Employing high-throughput screening of FDA-approved compounds we recently identified drugs capable of robust induction of sodium iodide symporter (NIS) activity to promote RAI uptake1. In particular, a leading drug candidate – the well-established anti-alcoholism drug disulfiram (DSF) – had no...

New targeted drug strategies are urgently needed to improve radioiodine uptake and efficiently ablate thyroid cancer cells thereby minimising the risk of recurrent disease. High-throughput screening (HTS) offers a promising approach to identify new candidate drugs that will induce sodium iodide symporter (NIS) function to promote iodide uptake. However, significant progress has been limited by a lack of thyroid cell-based assays amenable to HTS. Here, we constructed a thyroid ...

Thyroid cancer is increasing in incidence worldwide. While outcomes are generally good, up to 25% of patients suffer recurrence, and this has a significant impact on their quality of life and life expectancy. We hypothesised that thyroid tumours which recur display a distinct pattern of driver events, present on initial histology. Controlled-access TCGA data on thyroid cancer were downloaded and whole exome sequencing data analysed. An analysis pipeline utilising Platypus, Ann...

Successful responses to radioiodine treatment in differentiated thyroid cancer ultimately depend on uptake via the sodium-iodide symporter (NIS). However, many tumors exhibit NIS dysregulation, resulting in a poorer prognosis. Since breast cancer can also overexpress NIS, albeit of limited function, radioiodine treatment may be a promising treatment option. Our previous data show that overexpression of the pituitary tumor-transforming gene-binding factor (PBF) is partially res...

Dysfunctional regulation of sodium-iodide symporter (NIS) trafficking can result in ineffective radioiodide uptake in patients with differentiated thyroid cancer. Understanding the trafficking pathways of this key protein can be used to optimise radioiodide therapy. Recently, we identified via HiLo microscopy that the protein ADP-ribosylation Factor 4 (ARF4) helps shuttle NIS to the plasma membrane. To understand how ARF4 interacts with NIS mechanistically, we utilised advance...

The incidence of thyroid cancer is rapidly increasing worldwide. Whilst outcome in thyroid cancer is generally good, up to 25% of patients develop recurrence, and have a significantly reduced life expectancy. We hypothesise those thyroid tumours which subsequently recur display a distinct pattern of driver events. Whole exome sequencing data were downloaded from The Cancer Genome Atlas (TCGA). Bioinformatic analysis of data on N=43 patients whose tumours recurred was ...

In thyroid cancer, a reduction in sodium iodide symporter (NIS) expression at the basolateral plasma membrane (PM) of thyrocytes decreases the efficacy of radioiodine imaging, ablative therapy and treatment of metastases. NIS overexpression in breast cancer has resulted in radioiodine being widely proposed as a novel therapeutic strategy. However, uptake is insufficient for tumour destruction. Augmenting NIS PM localisation represents an important therapeutic strategy for incr...

By exploiting the canonical function of the sodium iodide symporter (NIS) ablative radioiodine therapy is an effective treatment for thyroid cancer. However, a subset of patients are unable to accumulate sufficient radioiodine for effective treatment due to the dysregulation of NIS, which can occur through decreased expression and/or reduced plasma membrane localisation. Although NIS localisation at the plasma membrane is critical for radioiodine uptake the mechanism of NIS tr...