Searchable abstracts of presentations at key conferences in endocrinology

ea0086oc6.2 | Thyroid | SFEBES2022

Enhancing radioiodide uptake by addressing the mechanism of sodium/iodide symporter (NIS) endocytosis

Zha Ling , Brookes Katie , Thornton Caitlin , Fletcher Alice , Kim Jana , Sunassee Kavitha , Blower Philip J , Nieto Hannah R , Smith Vicki E , Read Martin L , McCabe Christopher J

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...

ea0090oc11.1 | Oral Communications 11: Late Breaking | ECE2023

Copper-based therapeutics increase sodium/iodide symporter (NIS) transcription and enhance radioiodide uptake in thyroid cancer cells

Brookes Katie , Zha Ling , Kim Jana , Small Benjamin , Kocbiyik Merve , Manivannan Selvambigai , Kannappan Vinodh , Wang Weiguang , Sunassee Kavitha , Blower Philip , Nieto Hannah , Smith Vicki , Read Martin , Mccabe Christopher

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...

ea0094oc2.1 | Endocrine Cancer and Late Effects | SFEBES2023

Manipulating NIS endocytosis as a druggable target to enhance radioiodide uptake and prognostic indictor of thyroid cancer recurrence

Read Martin , Brookes Katie , Zha Ling , Manivannan Selvambigai , Kim Jana , Firth George , Sunassee Kavitha , Blower Philip , Boelaert Kristien , Nieto Hannah , Smith Vicki , McCabe Christopher

Background: Diminished sodium iodide symporter (NIS) activity at the plasma membrane (PM) is frequently associated with suboptimal radioiodide (RAI) uptake and poor prognosis in differentiated thyroid cancer (DTC). Endocytosis is a key determinant of symporter activity, with our recent study demonstrating specific interaction of NIS with Adaptor Protein 2 (AP2) – a central player in endocytosis. Here, our objective was to determine whether NIS endocytosis...

ea0094oc7.1 | Thyroid | SFEBES2023

A copper-based metabolite of disulfiram upregulates sodium iodide symporter (NIS) gene expression to enhance thyroidal uptake of radionuclides in vivo

Brookes Katie , Zha Ling , Small Benjamin , Kim Jana , Manivannan Selvambigai , Thornton Caitlin , Kannappan Vinodh , Wang Weiguang , Nieto Hannah , Sunassee Kavitha , Blower Philip , Smith Vicki , Read Martin , McCabe Christopher

Introduction: New approaches to improve radioiodide (RAI) uptake are urgently required in RAI-refractory thyroid cancer. We previously identified disulfiram as a leading candidate to induce sodium iodide symporter (NIS) activity and promote RAI uptake. In vivo, DSF is metabolised to diethyldithiocarbamate (DDC) which binds metal ions. Here, we aimed to gain a mechanistic understanding of how DSF and it’s related metabolite Cu(DDC)2 imp...

ea0086oc2.6 | Endocrine Cancer and Late Effects | SFEBES2022

Repurposing disulfiram as a therapeutic agent to enhance sodium iodide symporter activity in radioiodide therapy

Read Martin , Brookes Katie , Zha Ling , Kim Jana , Moolla Mehjabi , Kocbiyik Merve , Manivannan Selvambigai , Hoare Rachel , Kannappan Vinodh , Wang Weiguang , Sunassee Kavitha , Blower Philip , Nieto Hannah , Smith Vicki , McCabe Christopher

Background: New drug approaches are urgently needed that enhance radioiodide (RAI) uptake leading to efficient ablation of thyroid cancer, especially in RAI-refractory disease. We recently utilised high-throughput screening and identified FDA-approved compounds that induce sodium iodide symporter (NIS) function to enhance iodide uptake, including the proteasomal/ VCP inhibitor disulfiram. In vivo, disulfiram is rapidly metabolized to diethyldithiocarbamate (DDC), whic...

ea0101ps2-11-09 | Basic thyroid cancer research-1 | ETA2024

Dual agonism of sodium iodide symporter function in vivo

Brookes Katie , Zha Ling , Kim Jana , Wongsanit Sarinya , Small Benjamin , Nieto Hannah , Kannappan Vinodh , Wang Weiguang , Jhiang Sissy , Ringel Matthew , Campbell Moray , Sunassee Kavitha , Blower Philip , Boelaert Kristien , Smith Vicki , Read Martin , McCabe Christopher

Objectives: New approaches are urgently needed to enhance radioiodide (RAI) ablation of aggressive and metastatic thyroid cancer. Our previous experiments revealed that valosin-containing protein inhibitors (VCPi), such as disulfiram, markedly increase sodium iodide symporter (NIS) activity to promote RAI uptake. Recently, disulfiram was reported to inhibit NPL4 activity – a critical VCP cofactor – via its copper bound diethyldithiocarbamate metabolite Cu(DDC)2<...