Northwestern University recently developed neural stem cells (NSCs) that could be utilized with a human epidermal growth factor receptor 2 (HER2) inhibitor drug called tucatinib. According to the study, the fusion improved the survival rate in mice subjects induced with HER2-positive breast cancer brain metastases.
HER2 Inhibitors in Breast Cancer Brain Metastases
A surgeon prepares the spine of a patient affected by a metastatic breast cancer prior to use a Loop-X robotic-assisted surgery installation to secure the work on it, on June 10, 2021 at the University-affiliated hospital (CHU) in Angers, western France. - The Loop-X robotic-assisted surgery installation is a premiere in Europe.
The recent study on HER2 inhibitors was led by the institute's Feinberg School of Medicine experts. The study presented how the therapeutic utility of modified NSCs are administered for brain tumors. In addition, the research showed how the novel approach could be a better choice for therapy that could combat HER2-positive breast cancer brain metastases.
Brain metastases are a condition that is considered the leading cause of death in breast cancer patients. Although many studies are revolving around the correlation between brain metastases and breast cancer, the scientific community still lacks evidence. It hinders the discovery of potential solutions that could improve the outcome in individuals struck by the illness.
Clinical trials to examine how the blood-brain barrier reduces the efficacy of available therapies today are still too few. The missing data somehow stalls the progress to ease the concern and control the spread of the illness.
Overexpression of HER2 was identified in approximately 30 percent of breast cancer patients. The detection is commonly linked with advanced disease and a significant loss of chances for survival. Fifty percent of people struck with overexpressed HER2-positive breast cancer are most likely to develop central nervous system metastases. And unfortunately, this group is usually predicted with an average survival rate of 11 to 18 months after diagnosis.
Chemotherapy drugs were found to improve the outcome in primary breast cancer and systematic metastases patients throughout the oncology studies. However, the experts hope for a more effective solution to treat the problem.
Feinberg School of Medicine's Department of Neurological Surgery and Northwestern Medicine Malnati Brain Tumor Institute of the Lurie Comprehensive Cancer Center expert Alex Cordero authored the study along with colleagues.
Cordero said in a NewsMedical report that the systemic chemotherapeutic agents are challenged during passage whenever administered to the brain. Through their study, a new approach must be developed in order for the medical community to relay therapeutic regimens properly and have a novel delivery platform that could potentially improve outcomes during procedures for brain metastases.
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Efficacy of HER2 Inhibitor Drug Tucatinib
The latest study consisted of engineering the human-derived NSCs to deliver higher amounts of antibodies inhibiting HER2. The process was deliberately conducted through a continuous secretion of the antibodies while protecting the cell stemness, tumor-tropic, and migration properties.
Laboratory experiments in vitro showed that after treatment of HER2-positive breast cancer cells with NSCs, induced anti-HER2 antibodies blocked tumor proliferation through PI3K -Akt signaling pathway inhibition. The process observed was essential for cell growth and tumor survival.
In vivo examination was presented through injection of HER2-positive breast cancer and brain metastases in mice subjects to mirror the tumor cells throughout the arteries of a human patient. The specimens were then administered to either NSC control, anti-HER2 NSC's, and placebo treatments combined with tucatinib. The process of intake was carried out for 24 consecutive days through oral consumption.
The study concluded that the subjects who were able to receive the anti-HER2 stem cells combined with tucatinib had more chances of survival rate compared to subjects who were treated with control cells or placebo with tucatinib. The research was published in PNAS, titled "Combination of tucatinib and neural stem cells secreting anti-HER2 antibody prolongs survival of mice with metastatic brain cancer."
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