New cancer treatment targets from inside the cell

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

Associate Professor Mat Francois said the team developed a new approach to drug design. The new approach targets a molecular switch that was previously considered inaccessible.

“Current cancer treatments target elements on the outside of cancer cells. This 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. We do this by targeting the activity of transcription factors. These operate as a molecular switchboard inside cells and bind to DNA, turning gene expression on and off as needed.”

Dr Francois said the team 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. This 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. Being able to block access to these vascular highways with the flick of a molecular switch is a critical step to limit cancer metastasis.”

A collaborative effort

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.”

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

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

The original news article on the discovery can be viewed 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 that amount to AUD 6.7 million.