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February 2021

Improving treatment for metastatic breast cancer

Research led by the Peter MacCallum Cancer Centre is helping explain the broader effects of a new and powerful class of anti-cancer drugs, in the hope of making them work longer for breast cancer patients.

Cyclin-dependent kinase (CDK4/6) inhibitors have become a mainstay of treatment for metastatic breast cancer, though many patients eventually develop resistance.

Studies led by Dr Shom Goel have provided important insights into the broader activity of these drugs, which block key enzymes that breast cancer cells depend on.

‘The main effect of these drugs is like pulling a handbrake, such that breast cancer cells stop dividing and enter a paused state that we call ‘senescence’,’ said Dr Goel, a consultant oncologist and group leader in Peter Mac’s cancer research division.

‘Although CDK4/6 inhibitor drugs are very effective they don’t kill cancer cells and, for many patients, their effects can wane over time.

‘There’s a great need to extend the window where these drugs provide good cancer control.’

The preclinical studies demonstrate for the first time that the inhibitor drugs – in addition to blocking cancer cell division – trigger widespread epigenetic changes in breast cancer cells.

For example, the cells developed new ways to avoid cell death (apoptosis) and became more visible to the immune system.

‘These epigenetic changes completely transform the way the cancer cells look and behave,’ said Dr Goel.

‘And this new understanding is important because as the cells change, they develop new vulnerabilities that we can possibly exploit.

‘For example, our research supports trialling CDK4/6 inhibitors in combination with other treatments – such as immunotherapies or with new therapies designed to trigger cell death – and this could be how we achieve more durable responses.’

The CDK4/6 inhibition reprograms the breast cancer enhancer landscape by stimulating AP-1 transcriptional activity research paper is published in the Nature Cancer journal.

•       Read the research paper at https://www.nature.com/articles/s43018-020-00135-y.