Neural Stem Cell Therapy for Breast Cancer Brain Metastases
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Today, breast tumors can be detected early and removed with advanced surgery and treatment, but current therapies cannot prevent or eradicate breast cancer after metastatic spread to distant organs. The prognosis is very poor if breast cancer spreads to the brain. As a shielded “sanctuary site,” the brain may harbor breast cancer cells which resist current treatments and can develop into satellite tumors, known as metastases, long after chemo-, radiation, or immuno- therapies have been applied. The patient’s situation can be managed in the clinic only for a few weeks or months before becoming fatal. Our project seeks to provide new hope for patients, as we will try to inhibit breast cancer brain metastases through an innovative approach based on stem cells, the body’s own natural mechanism for healing and regeneration.
 
 
 
 
 
 
 
 Our hypothesis is that brain metastases in breast cancer patients can be targeted with neural stem cells, which are known to seek out diseased or cancerous areas in the brain. We will determine where, when, how often, and in what number neural stem cells need to be administered to target breast cancer cells within the brain tissue. We will “arm” neural stem cells with a “pro-drug” strategy so they can locally convert a harmless drug into a highly toxic drug to eradicate breast cancer brain metastases. Finally, we will investigate whether treatment with neural stem cells is safe. We will track the neural stem cells, analyze how they behave in animal subjects, and examine if the administered stem cells affect any normal healthy tissues.
 
 
 
 
 
 
 
 We are collaborating with Dr. Evan Snyder at The Burnham Institute, who brings expertise in neural stem cells biology to this project. In preliminary work at Scripps, we have established human breast cancer cell and mouse models that mimic the development of brain metastases in breast cancer patients. We also have an armed neural stem cell model with documented therapeutic properties and a non-invasive imaging system that allows us to follow the breast cancer cells and stem cells in live mice to analyze their response to treatment. We will use female mice that accept human cells and inject them with our patient-derived breast cancer cells, which have a tendency to spread to the brain. The mice will be imaged repeatedly to find out when brain metastases have developed. Once that is the case, we will inject neural stem cells. These stem cells have been engineered to contain a “reporter gene” that allows us to track them in our mouse “patients” by imaging. The stem cells also contain an introduced protein that can convert a non-toxic pro-drug into its toxic form that kills dividing cells such as the tumor cells. Once the stem cells have migrated to the metastatic lesions, we will treat the mice with the harmless pro-drug. We expect that this will kill the tumor cells in the vicinity of the stem cells without affecting the normal brain cells or the stem cells themselves, as long as they do not divide. Should that be the case, however, the treatment will also kill the stem cells and thereby function as a built-in safety mechanism. The effects of this treatment will be followed through non-invasive imaging of the live mice and, later, at the cellular level under the microscope.
 
 
 
 
 
 
 
 The proposed project, if successful, will demonstrate for the first time that neural stem cells can be used to eliminate metastatic breast cancer cells that have spread to the brain. This would represent a breakthrough for treating advanced breast cancer.