Malignant Gliomas and Glioblastoma
Malignant gliomas and glioblastoma in particular, are the most common and malignant of all primary brain tumors. These brain tumors infiltrate the brain and are lethal. All malignant gliomas undergo the same non-curative treatment, including surgery, chemotherapy and radiation.

Precision Medicine applied to brain tumors: Personalizing the use of chemotherapy
Given that the molecular features of malignant gliomas are highly variable across patients, these tumors have been classified into different groups based on which genes are active or expressed. These molecular patterns and their underlying mechanisms might provide a unique tumoral vulnerability to treatments.

The regulation of brain tumor gene expression.
The lab is focused on exploring the mechanisms that brain tumors rely on to express genes that are important for cancer, and using these molecular features to personalize the use of chemotherapy for patients with malignant brain tumors.

scheme of network of master regulator transcription factors

Scheme of network of master regulator transcription factors that determine proneural gene expression during glioma progression (data from Sonabend et al., Cancer Research 2014).

Topoisomerase II (TOP2) is an enzyme that de-coils DNA. TOP2 is highly elevated in a subset of gliomas starting at early stages of tumor development. Our research team is exploring the role this enzyme plays in tumor development, including regulation of transcription.

Personalizing TOP2 targeting with chemotherapy for brain tumors.
There are multiple FDA-approved drugs such as etoposide that target TOP2, and we are investigating the mechanisms that determine the susceptibility of glioblastomas to these drugs. Our goal is to develop a test that will predict which patients might benefit from TOP2-targeting drugs, as some tumors are susceptible to these drugs whereas others are resistant.

Chemotherapy delivery into the brain: Thinking outside the box.
Given by traditional routes, etoposide does not reach tumor cells on patients’ brains at sufficient levels. In preclinical studies, Dr. Sonabend and colleagues showed that direct delivery of etoposide into the tumors is highly effective at inhibiting tumor growth. We are investigating novel means of delivery of these treatments directly into the brain including intratumoral delivery through convection-enhanced delivery (CED) and the use of nanoparticles to improve their efficacy while avoiding unnecessary side effects of these therapies.