Paula Foster, Robarts Research Institute: London, Ontario

Project Title: “In Vivo MRI Characterization of Changing Blood-Tumour Barrier Permeability in a Mouse Model of Brain Metastasis”

What does the title mean?

This research focuses on the cells responsible for blocking treatment to the brain, specifically multi-drug resistant glioblastoma multiforme

Project Summary

The most common tumours in the central nervous system are metastases originating from lung and breast cancer. Brain metastasis occurs in 15-25% of metastatic breast cancer patients. A diagnosis of brain metastases is terrifying. Untreated, the median survival time is 2–3 months; aggressive treatment extends this only marginally, to 4–12 months.

The blood-brain barrier (BBB) tightly controls the passage of substrates from the blood into the brain and this hinders delivery of chemotherapeutics to metastatic tumours in the brain. When tumours develop the local BBB, sometimes referred to as the blood-tumour-barrier (BTB), can become leaky (or permeable). However, not all tumours are permeable. Within one individual there can exist both permeable and non-permeable tumours. This makes treatment very complicated.

In this project we are using a mouse model of breast cancer metastasis to the brain and advanced MRI tools to detect and monitor the leakiness of brain tumours over time in the whole brain. We expect our research will produce important information about what influences tumour growth and permeability in the brain. It is critical to understand the conditions that cause altered and heterogeneous BBB permeability in order to advance the development of treatments for brain tumours.

Final Report

Radiotherapy of the whole head is the standard of care for breast cancer patients with multiple brain lesions. While this treatment has been essential in the management of existing tumours, there are also many known negative effects associated with radiation of normal brain. In this study MRI was used to examine how radiotherapy of normal brain can effect the likelihood of growth of new tumours in an animal model of breast cancer brain metastasis. Imaging results showed that irradiated but otherwise healthy brain had an increased ability to support the growth of cancer. Investigating the impact of radiotherapy on normal brain could have implications in clinical patient management, particularly in patients with brain cancer that is resistant to radiotherapy or pre-existing cancer elsewhere in the body.

Publications

Cranial irradiation increases tumour growth in experimental breast cancer brain metastasis
Amanda M. Hamilton, Suzanne M. Wong, Eugene Wong, Paula J. Foster
January 2018
NMR in Biomedicine