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New approach to cancer treatment design

February 22, 2017

Researchers at the Institute for Molecular Bioscience (IMB), University of Queensland, have found a promising small molecule treatment in a pre-clinical study of breast cancer.

Associate Professor Mat Francois said the team had developed a new approach to drug design by targeting a molecular switch previously considered inaccessible.

“Current cancer treatments target elements on the outside of cancer cells, which limits our ability to control specific activity happening inside the cell,” Dr Francois said.

“Our new approach to drug design allows us to cross this barrier and get inside the cell by targeting the activity of transcription factors, which operate as a type of molecular switchboard inside cells and bind to DNA to turn gene expression on and off as needed.”

Dr Francois said the team discovered a small molecule called Sm4 that demonstrated it could successfully use this approach to fine tune the cellular activity responsible for cancer-induced vessel growth, a key contributor to cancer metastasis.

“The small molecule we have discovered, Sm4, has shown it can target and switch off the activity of transcription factor SOX18, which controls the development of our blood and lymphatic vessels induced by cancer growth.”

“These vessels act as an on-ramp system to carry cancer cells throughout the body, so being able to block access to these vascular highways with the flick of a molecular switch is a critical step to limit cancer metastasis.”

In a pre-clinical study of breast cancer, performed in collaboration with QIMR Berghofer Medical Research Institute, Dr Francois said the team found that mice treated with Sm4 had significantly improved survival rates.

“Our results show that targeting the transcription factor SOX18 with a small molecule compound is a promising new molecular strategy to treat cancer metastasis.”

“Given that high levels of SOX18 have also been associated with poor prognosis for cancer in human patients, it is exciting to know that we have identified a small molecule inhibitor that could help improve cancer treatment.”

The study was published in eLife and involved research teams from Australia, the UK, the US and China.

The original  news article on the discovery was published on the IMB website.

The Australian Cancer Research Foundation has supported IMB by providing four grants, totalling AUD 7.1 million, towards cutting edge cancer research equipment and technology. The Foundation has also supported cancer research at QIMR Berghofer by providing three grants, totalling AUD 6.7 million.

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