Targeting the Achilles' heel of breast cancer

By Adam Florance
Friday, 04 August, 2017

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While treatments for breast cancer have improved considerably in recent years, there has been little advancement in combating triple-negative breast cancers, which affect as many as one in three of Australian women suffering this debilitating disease.

A team of researchers from Melbourne’s Walter and Eliza Hall Institute have found that by combining traditional treatments with a new class of anticancer agents they can target the ‘Achilles’ heel’ of HER2-positive breast cancers, in the first significant improvement in this area in over 30 years.

Triple-negative, or HER2-positive, breast cancers are among the most aggressive types of breast cancer. This new research has found that by combining existing treatments with S63845, an anticancer compound developed by pharmaceutical company Servier, promising results have been achieved.

Lead researcher Dr Delphine Merino said: “Combining S63845 with standard therapies such as chemotherapy, or targeted drugs such as Herceptin, proved highly effective in killing these very aggressive tumour types.”

This new compound is an MCL-1 inhibitor, a promising new class of anticancer drugs that targets the so-called Achilles’ heel of the cancer, triggering tumour cell death.

Professor Geoff Lindeman, from the Peter Mac and Royal Melbourne Hospital, said: “Our hope is that it will be possible to combine MCL-1 inhibitors with conventional therapies to more effectively treat certain types of breast cancer and deliver better outcomes for our patients.”

This research utilised patient-derived tumours, which are an invaluable way to develop anticancer drugs, according to Dr François Vaillant of the Walter and Eliza Hall Institute.

“With the support of the Victorian Cancer Biobank, and samples donated by breast cancer patients, we have generated a large number of laboratory models that mimic how tumours behave and respond to therapy in the patient, allowing us to test a range of anticancer drugs,” he said. “This approach can help fast-track the development and transfer of promising drugs to the clinic.”

While triple-negative breast cancer is most common among women with a faulty BRCA1 gene, it is the MCL-1 protein that allows cancer cells to survive traditional treatments. Dr James Whittle, a PhD student at the Olivia Newton-John Cancer Research Institute, explained: “MCL-1 gives cancer cells a survival advantage, allowing them to resist chemotherapy or other anticancer therapies that would otherwise trigger cancer cell death.

“Importantly, the combination of the MCL-1 inhibitor S63845 with standard therapies was far more effective than either treatment alone. These can be incredibly aggressive tumours, so to see a response to the combined therapy in this tumour type is very exciting.”

Published in Science Translational Medicine, this research was led by the Walter and Eliza Hall Institute in collaboration with Servier. It was supported by the National Health and Medical Research Council, the Australian Cancer Research Foundation, the Joan Marshall Breast Cancer Research Fund, the National Breast Cancer Research Foundation, the Qualtrough Cancer Research Fund, the Victorian Cancer Agency and the Victorian State Government Operational Infrastructure Support Program.

Image credit: © Olson

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