A new research study from the CBTP lab entitled “Combined Targeting of PI3K and MEK Effector Pathways via CED for DIPG Therapy,” was published in Neuro-Oncology Advances on May 29, 2019. The published manuscript, submitted by Dr. Uday Maachani (Dr. Souweidane Lab) on behalf of the entire research team, showed the results of a comprehensive study of midline gliomas including diffuse intrinsic pontine gliomas (DIPG), and the relationship between amplified phosphatydylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MEK), and the development of these particular tumor types.
In this comprehensive study, the research team tested both PI3K inhibitor ZSTK474 and MEK inhibitor trametinib, alone and in combination in vitro and in vivo, using various delivery methods.
The results showed that combination treatments were found to be synergistic with dosing across the cell lines tested, and significant tumor suppression was seen when given systemically against a subcutaneous DIPG model, and when given via convection-enhanced delivery (CED) in an intracranial DIPG mouse model. Data indicates that ZSTK474 and trametinib combination therapy inhibits malignant growth of DIPG cells in culture and in animal models, prolonging survival. The results warrant further investigation and the team is excited by the potential for a promising new combination approach to treat DIPG via CED.
Funding: This research was supported in part by Cristian Rivera Foundation, McKenna Claire Foundation, The Lyonhearted Foundation, Christian Koehler Foundation, Brooke Healey Foundation, Fly a Kite Foundation, Children’s Brain Tumor Family Foundation, Joshua’s Wish, Lily LaRue Foundation, and by the Alex Lemonade Stand Foundation’s Pediatric Oncology Student Training Grant (UT), and American Brain Tumor Association Medical Student Summer Fellowship in honor of Collegiate Charities Dropping the Puck on Cancer and Super Lucy (RC).