Discipline: Biological Sciences
Subcategory: Cancer Research
Sarea Recalde Phillips - Pennsylvania State University
Co-Author(s): Huy Tram N. Nguyen, University of Wisconsin-Madison,Madison, WI; Paul Clark, University of Wisconsin-Madison,Madison, WI; John S. Kuo, University of Wisconsin-Madison,Madison, WI
Glioblastoma (GBM) is the most frequently diagnosed adult primary brain cancer, associated with less than 2 years median survival despite current aggressive therapies. Tumor treating fields (TTFields) emit low-to-moderate intensity alternating electrical fields to treat a localized tumor area, disrupt the mitotic spindle, and impede microtubule formation and cell division. TTFields combined with microtubule-inhibiting drugs (i.e. cabazitaxel) may improve clinical outcome. Since both TTFields and cabazitaxel target microtubule formation in cells, combining the treatments may synergize to decrease GBM proliferation.
The effects of the combined treatment were tested on two independent patient-derived glioblastoma stem-like cell lines (GSC). Initially, a cabazitaxel dose response curve was used to determine the IC50 for each GSC line, which we found to be 0.03nM. The effects of combined treatment of cabazitaxel (dose range = 0nM to 0.06nM) with TTF was tested on GSC lines as follows to assess therapeutic effect: GSC were treated with both cabazitaxel and TTFields for seven days, then seeded for clonogenic sphere assay for three weeks. The number of tumor spheres were then counted and compared with the control groups of treatment with only cabazitaxel.
Our results demonstrated the combined TTField/cabazitaxel treatment caused a more significant reduction in both cell lines’ proliferation assay and quantitative GSC sphere assay than single treatments alone. This study suggests that combining TTField with cabazitaxel is a promising new approach for GBM treatment.
Funder Acknowledgement(s): The UW Carbone Center's Pilot Grant The Roger Loff Memorial Fund for GBM Research Semman Gray Matters Jam Steve Bolser Joggin for Noggin fund NSF Award 1659159 NIH Grant 5R25NS083065-05
Faculty Advisor: Dr. John S. Kuo, firstname.lastname@example.org
Role: I was responsible for culturing and passaging the two patient lines used during the project. I performed a preliminary dose response assay of the cell lines with varying cabazitaxel concentrations to establish the IC50. I then exposed the GSCs to cabazitaxel, TTFields, or a combination of the two in a proliferation assay. Following the completion of this assay, I performed a subsequent sphere assay and quantified the amount of spheres formed from the various treatment methods generated to evaluate the effect of the combinatory treatment to a monotherapy of either the TTFields or cabazitaxel.