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Targeted Sensitization of Glioblastoma Multiforme Using AAAPT Technology
Megan Mendieta1, Naze G Avci1, Raghu Pandurangi2
1University of Houston Houston TX 77204 USA.
Abstract:
Glioblastoma Multiforme (GBM) is the most malignant type of all brain tumors. Current GBM treatment options include surgery, followed by radiation and chemotherapy. However, GBM can become resistant to therapy, resulting in tumor recurrence. GBM cells develop resistance to treatments by either downregulating cell death pathways (CD95) or upregulating cell survival pathways (NF-κB (p65)). Healthy tissues can be affected by the increased therapeutic dose. Therefore, it is important to develop a method that can only target GBM tumor cells, thereby reducing the non-specific uptake which will reduce the side effects. Here we demonstrate an application of novel priori activation of apoptosis pathways of tumor technology (AAAPT), which has been used to demonstrate the effect of targeted tumor sensitizers to make chemotherapy work at lower doses in breast, lung and prostate cancers. Treatment of GBM spheroids with AAAPT in 3D PEGDA microwells, showed an increase in cell death, an upregulation of cell death pathways, and a downregulation of cell survival pathways, in comparison to Temozolomide (TMZ), an oral alkylating agent, which is a commonly used chemotherapy in the treatment of GBM. The dose of AAAPT sensitizers may provide a promising method to increase treatment efficacy and reduce off-target toxicity, as an alternative to existing methods which cause significant off-target damage.
Insights
A novel priori activation of apoptosis pathways of tumor technology (AAAPT) shows promise for treating glioblastoma multiforme (GBM). This targeted approach increases GBM cell death and reduces side effects compared to traditional chemotherapy.
Area of Science:
- Oncology
- Biotechnology
- Cancer Research
Background:
- Glioblastoma Multiforme (GBM) is an aggressive brain tumor with limited treatment options.
- Tumor recurrence is common due to therapy resistance, involving downregulation of cell death (CD95) and upregulation of survival (NF-κB) pathways.
- Current treatments can cause significant off-target toxicity to healthy tissues.
Purpose of the Study:
- To evaluate a novel priori activation of apoptosis pathways of tumor technology (AAAPT) for targeted GBM treatment.
- To assess AAAPT's efficacy in inducing GBM cell death and modulating survival/death pathways.
- To compare AAAPT's effectiveness and toxicity profile against standard GBM chemotherapy.
Main Methods:
- Treatment of GBM spheroids using AAAPT within 3D PEGDA microwells.
- Analysis of cell death pathways (e.g., CD95) and survival pathways (e.g., NF-κB).
- Comparison with Temozolomide (TMZ), a standard chemotherapy agent for GBM.
Main Results:
- AAAPT treatment led to increased GBM cell death in 3D spheroids.
- AAAPT upregulated cell death pathways and downregulated cell survival pathways.
- Compared to TMZ, AAAPT demonstrated enhanced efficacy in targeting GBM cells.
Conclusions:
- AAAPT offers a promising targeted approach to increase glioblastoma treatment efficacy.
- This technology has the potential to reduce off-target toxicity associated with conventional chemotherapy.
- AAAPT sensitizers may provide a viable alternative for GBM treatment, improving patient outcomes.
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