Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Neuroscience

Supervisor

Hebb, Matthew O.

2nd Supervisor

Schmid, Susanne.

Abstract

Brain metastases occur in 15-30% of breast cancer patients, severely impeding their survival of these individuals. As cancerous tissue is innately vulnerable to non-ablative electrical fields, our group aims to develop Intratumoral Modulation Therapy (IMT), a treatment that uses bioelectrodes to deliver electric fields to brain tumors and induce cancer cell death. We have previously shown primary brain tumor sensitivity to low-voltage, intermediate-frequency IMT, but the effect on secondary brain tumors has not been investigated. We aim to determine whether breast cancer brain metastases (BCBM) cells are susceptible to IMT in vitro, to show healthy nervous tissue is unaffected by IMT, and to develop a rudimentary rat model of human BCBM for testing IMT in vivo. Cell survival assays revealed BCBM cell sensitivity to IMT and healthy nervous tissue resistance to the treatment. Rats successfully grew human BCBM. Novel treatments for BCBM are needed and IMT holds potential.

Summary for Lay Audience

Brain metastases (BM) are tumors that form when cancer from another part of the body spreads to the brain. BM occur in 15-30% of breast cancer patients and severely impede survival due to limited treatment options. Therefore, new therapeutic approaches are needed to tackle these deadly tumors. Many types of cancer cells are vulnerable to electric fields (EF) with specific properties. These EFs target actively dividing cells, and as healthy nervous tissue does not actively divide, these fields should not harm non-cancerous brain cells. Our research group is focused on developing Intratumoral Modulation Therapy (IMT), a promising new treatment that uses implantable electrodes to deliver EF directly to brain tumors to promote cancer cell death. These effects of IMT have been successfully demonstrated on glioblastoma, a tumor that originates in the brain, but the impact of the therapy on BMs has not been investigated. The first aim of this study is to test whether breast cancer brain metastases (BCBM) cells are vulnerable to IMT fields. The second aim is to show that healthy nervous tissue is unaffected by IMT treatment. The last aim is to inject human BCBM cells directly into rat brains and demonstrate that these tumors can be grown in a host as the first step to translating our therapy to animal trials. BCBM cell populations subjected to IMT were discovered to have less live cells compared to untreated populations and non-cancerous nervous tissue was not affected by the treatment. The rats did not reject human BCBM cells and tumors grew to the size necessary to test IMT in a live organism. There are currently no specific treatments that target BCBM and novel therapies must be developed. Therapies for non-cancerous conditions, such as chronic pain, epilepsy, and movement disorders, involving implantable electrodes have proven to be safe and provide support for potential clinical use of IMT. The direct delivery of EFs to brain tumors has the potential to promote cancer cell death, prevent reoccurrence, and support patient quality of life. This project will yield key information needed to advance the development of IMT towards clinical application for BCBM.

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