Using inhibitors of valosin-containing protein to increase radioiodide uptake in combination with in vivo NIS-mediated gene therapy
Caitlin Thornton, University of Birmingham
The success of radioiodide treatment for differentiated thyroid cancer hinges upon adequate uptake of iodide by malignant thyroid follicular cells. We recently discovered two protein interactors of the protein mediating iodide uptake, NIS: ARF4 and VCP. ARF4 binds to NIS and increases its localisation at the plasma membrane (PM), whilst VCP targets NIS for proteasomal degradation. Using drugs which inhibit the function of VCP our group has shown that iodide uptake is improved, indicating that these may be useful in potentiating radioiodide treatment for differentiated thyroid carcinoma.
Professor Christine Spitzweg is the world leader in the delivery of the sodium-iodide symporter to non-thyroidal and thyroidal carcinomas, and is currently investigating restoring and improving iodide uptake in radioiodide refractory thyroid carcinomas. This unique approach utilises a novel polyplex gene delivery system to deliver the exogenous NIS gene to cancer cells so they become sensitized to radioiodide therapy.
We aim to build collaborative links with the Spitzweg lab in Munich through a 10 week research placement during which we will converge our in vitro data showing that we can therapeutically inhibit VCP to enhance NIS function at the PM with their in vivo ability to target exogenous NIS function as an entirely new therapeutic direction.
Grant awarded: £1,900