Scientific Presentations Summer 2009 - Dana-Farber/Harvard ...

Targeting Glioma Growth
Cody Cameron
Mentor: Khalid Shah, PhD
Scientific Advisor: Tugba Bagci, PhD
Massachusetts General Hospital
Glioma is a form of brain cancer which results in very sudden yet detrimental effects
to the patient. Like most cancers, gliomas result from the deregulation of certain
components of the cell cycle, such as proliferation. While normal cells regulate their
proliferation and undergo apoptosis when damaged, glioma cells undergo uncontrolled
proliferation, thereby creating neoplasms. Among other pathways, the PI3
Kinase-Akt pathway is commonly mutated in gliomas resulting in uncontrolled
proliferation. Over activation of PI3 Kinase leads to increased phosphorylation and
thereby activation of Akt, which then leads to increased cell growth. The inhibition
of activity along the PI3 Kinase pathway can achieved with a new drug, PI-103. The
overall goal of the project is to test the efficacy of PI-103 alone and in combination
with stem cell based pro-apoptotic therapies in both malignant and invasive glioma
cells in vitro as well as in mouse models of glioma. My part in the project is to test the
effect of PI-103 on the PI3 Kinase pathway components in different glioma cells in
culture. Specifically, I aim to demonstrate the changes in the phosphorylation of Akt
levels in response to different doses of PI-103 treatment in six established and two
primary human glioma cell lines. My results will determine whether this drug will
inhibit the activation of the PI3-kinase-Akt pathway in human glial cells. This should
set up a clear-cut plan for in vivo experiments that will follow in culture studies and
will be subsequently performed in the laboratory.