Searchable abstracts of presentations at key conferences in endocrinology

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...

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<...