Novel approaches to targeting metastasis in breast cancer

Lead Academic: Thomas A Hughes (Leeds)
William J Brackenbury (York)
Ingunn Holen (Sheffield)
Substantial complementary expertise in breast cancer exists across the White Rose consortium, however, collaboration across all three universities has not previously been realised. Partnership between these centres, combining the range of high-level expertise available has potential to be sector leading.  We propose to share expertise in order to explore further the novel potential therapeutic targets that are the expertise of the Brackenbury lab, the Voltage-Gated Sodium Channels (VGSCs), with the aims of generating pilot data to support a subsequent larger collaborative project application, and initiating and maintaining cross-Yorkshire collaboration in breast cancer research.
VGSCs regulate electrical excitability and migration during central nervous system development. Brackenbury has recently shown that VGSCs are up-regulated in breast cancers and promote growth, invasion and metastasis of tumours in mice. In addition, VGSCs contribute to the relatively depolarised membrane potential that is characteristic of breast cancer cells, which may in turn regulate cellular proliferation and migration. Importantly, the VGSC-blocking antiepileptic drug phenytoin inhibits sodium current, tumour growth and metastasis. These findings suggest that VGSCs may be novel therapeutic targets in breast cancer. However, the potential benefits of combining VGSC inhibition with conventional therapies for either primary or – more critically – metastatic breast cancer have not been explored. Using complementary expertise across the three universities, we will test the hypothesis that combining VGSC inhibitors with standard breast cancer therapies has synergistic benefits in breast cancer treatment.
Other people involved with the project
Valerie Speirs, Mihaela Lorger (Leeds)
Ming Yang (York)
Penelope Ottewell (Sheffield)

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