Putting the brakes on bowel cancer

For clinicians, detecting cancer is a victory in itself, but stopping its spread is crucial to a successful outcome. For Professor Ron Firestein, 2021 brought welcome results in that endeavour, thanks to the discovery that disabling two proteins together robs bowel cancer cells of their ability to express genes necessary for growth and spread.

Australia has one of the highest rates of colon cancer in the world — one in 13 Australians will develop the disease in their lifetime — and it is the nation’s second deadliest cancer.

The research, published in the journal Molecular Cell, marks a significant step in the understanding of how the transcription machinery process works in cancer cells.

“In total, this work has found the ‘two brake pads’ that when pressed together stops cancer gene expression and growth,” Prof Firestein says.

“This research could have far-reaching impacts beyond bowel cancer, showing that cancer cells are fundamentally evasive and utilise multiple paths to become malignant,” he says.

New targeted therapies for bowel cancer

In a separate study with Dr Chunhua Wan, using Nobel Prize-winning genetic screening technology to identify new targets for bowel cancer tumours, the researchers discovered that a gene associated with leukaemia is also involved with bowel cancer.

Trialling two agents that inhibit the gene KMT2A, Prof Firestein and Dr Wan saw how they blocked bowel cancer growth and self-renewal, with very little damage to normal cells.

Realising that very similar drugs are currently in clinical trials to treat acute myeloid leukaemia, the team knew they had uncovered a promising potential treatment option, and published their important findings in Sciences Advances, May 2021.

“Due to limited therapeutic options, bowel cancer patients, especially those diagnosed at late stages, have very poor outcomes,” Prof Firestein says. ”These findings may pave the way to developing new targeted therapies for bowel cancer patients.”

Targeted therapy is a relatively new way of treating bowel cancer. It has many advantages over conventional therapies such as chemotherapy and radiotherapy, as it only affects cancer cells, is better tolerated by patients, and has fewer side effects.

Funders | Evans Family; National Health and Medical Research Council (NHMRC)

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