Examining the in-vitro effect of UNC6934 & BI-9321 alone and in combination with ONC201 on Diffuse Intrinsic Pontine Glioma (DIPG) cells

Author

Ross BuchmanFollow

Date of Completion

2022

Document Type

Honors College Thesis

Department

Biochemistry

Thesis Type

Honors College, College of Arts and Science Honors

First Advisor

Dr. James Stafford

Second Advisor

Dr. Matthias Brewer

Third Advisor

Dr. Jay Silveira

Keywords

DIPG, Cancer, Epigenetics, H3K36me2, UNC6934, BI-9321

Abstract

Diffuse Intrinsic Pontine Glioma (DIPG) is an aggressive pediatric brain cancer with little chance of survival and no effective treatment options. Recently, a new drug, ONC201, has had success in certain DIPG patients by targeting the metabolism of the tumor. In parallel, the study of how gene expression is regulated in DIPG (e.g., epigenetics), has revealed other unique targets that may hold promise for treating DIPG. This study focused on two drugs, UNC6934 & BI-932, which were expected to antagonize critical epigenetic, regulatory proteins in DIPG thereby decreasing viability of these tumors. Both drugs decreased cell viability of DIPG cells in vitro. The half maximal inhibitory concentration (IC₅₀) for UNC6934 treatment of DIPG cells in vitro was determined to be 17.99 µM, while the IC₅₀ for BI-9321 was 88.93 µM. A key feature of both these drugs is that their effect on the cell viability of fibroblast cells was less than their effect on DIPG cells. This difference reveals that the therapeutic index of these drugs is better for DIPG as compared to fibroblasts. Combinatorial treatment of ONC201 with UNC6934 was shown to decrease cell viability of DIPG cells in vitro beyond either drug alone, suggesting an additive effect. This additive combination could reveal a potential for using these drugs in combination to treat DIPG. These preliminary results support future research into the mechanism of action of these drugs and their potential use in combination with ONC 201.

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Recommended Citation

Buchman, Ross, "Examining the in-vitro effect of UNC6934 & BI-9321 alone and in combination with ONC201 on Diffuse Intrinsic Pontine Glioma (DIPG) cells" (2022). UVM Honors College Senior Theses. 524.
https://scholarworks.uvm.edu/hcoltheses/524