BDRF research could improve chemoradiotherapy efficacy

A BDRF study is examining whether levels of a specific protein in rectal cancer can predict the effectiveness of radiotherapy.

The gold standard treatment for rectal cancer is surgical removal, but many tumours are caught at a stage where they need to be shrunk down with chemo & radiotherapy first. In some cases, radiotherapy can destroy the tumour entirely. Good responses to these treatments vastly increases the likelihood of survival for patients, and sometimes mean they can avoid surgery entirely.

There is compelling evidence that if high amounts of a protein called Nrf2 are present in a tumour, it will be more resistant to these neo-adjuvant therapies. Previous studies have shown however that exposure to a drug known as Brusatol, which inhibits Nrf2, makes lung cancer cells more sensitive to radiotherapy.

Our project, based at Liverpool University’s Institute of Translational Medicine, seeks to definitively prove that high levels of Nrf2 in rectal tumours reduce the effectiveness of radiotherapy. It will look at tissue samples from tumours subsequently treated to assess levels of Nrf2 against the outcome of the treatment. The team will also use genetically modified artificial cell lines to compare responses to radiotherapy in cells with high and low levels of Nrf2.

A successful outcome to this work would be extremely exciting. Not only would we be able to personalise care by predicting the likelihood of a successful outcome to neoadjuvant treatment, but also to identify patients who may benefit from treatment with Brusatol to enhance the benefit of radiotherapy.

Proof of Nrf2’s role in stopping cancers responding to radiotherapy would pave the way to major clinical trials of Brusatol as an enhancer of chemo & radiotherapy.

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