New Preclinical Model Developed in Melbourne to Study Cancer Metastasis

Whilst primary breast cancer treatment is usually successful, treatment becomes much more difficult after the cancer has spread to other organs (metastasised). In particular, when breast cancer spreads to the brain, it can use the protection of the “blood-brain barrier”. The blood-brain barrier is a natural selective membrane which surrounds the brain and stops large molecules and microorganisms (such as bacteria from infections) from moving from the blood into the secure ecosystem of the brain. Unfortunately, the barrier can also block drugs from being able to access the cancer cells within.

Brain metastasis can be relatively common in some forms of breast cancer. As new drugs are developed, it is important to assess whether they are able to prevent this brain metastasis. However, to date this has been challenging due to a lack of appropriate preclinical models that mimic the metastatic process from the breast to the brain.

To address this gap, NBCF-funded researcher Dr Normand Pouliot (Olivia Newton-John Cancer Research Institute) and his team have developed a new mouse model of HER2-positive breast cancer. In this model, the cancer will metastasise from the mouse mammary gland (breast) to brain tissue, giving researchers a model in which to try and stop the spread with new drug therapies. The model closely mimics the entire series of events that occur during the spread of human HER2-positive breast cancer, making it an invaluable tool for research and drug development.

Dr Normand Pouliot

Dr Pouliot and his team have now used this novel mouse model to test a new drug for HER2-positive breast cancer, called neratinib. In their study, published in the international journal Breast Cancer Research, they showed that neratinib was effective at reducing tumour growth when the drug was used before surgery in the mouse model. Importantly, cancer spread was significantly reduced in mice treated with neratinib and, in particular, none of the treated mice developed brain metastases. Moreover, the treated mice also had longer disease-free survival. Although further study and clinical trials are needed, the results indicate that neratinib may form part of a novel therapeutic strategy to help prevent breast cancer growth and metastasis in the future.

“Overall, the results from our study indicate that the new mouse model recapitulates the spread of aggressive HER2-positive breast cancer to the brain as seen in patients, and provides a unique opportunity to study molecular markers and novel therapeutics that might prevent this spread,” said Dr Pouliot. “We are grateful to NBCF supporters and their kind donations that support our work, which will have significant impact on future drug development studies.”