Glioma stem cells have been described as tumor cells that behave like stem cells (self-renewal and multipotency), with enhanced resistance to chemotherapy and radiation compared to non-stem cells. The glioma stem cells are likely to be the source of cells from which a tumor regrows after therapy. At The Friedman Brain Institute, we are pioneering new avenues of glioma research by defining subsets of glioma stem cells in mouse transplant studies with viral lineage markers, which will lead us to understand molecular programs that control renewal and survival of cancer stem cells. Armed with this knowledge, we plan to design novel clinical interventions that will improve outcomes for glioma patients.

Scientists in this research area include:

• Roland Friedel, PhD
• Thomas O'Loughlin, PhD
• Nadejda Tsankova, MD, PhD
• Hongyan ZouMD, PhD

Malignant gliomas are not only fast growing but also diffusely infiltrative in nature, the latter being responsible for their resistance to therapy and fast recurrence after surgical resection. Using a combination of computational and functional tools in primary human tissue samples and mouse models, we are actively investigating the biological drivers of glioma migration and invasion, and are developing rational targets for potential therapy. To this end, our group discovered TEAD1 as a critical regulator of glioma migration; demonstrated anti-invasive efficacy of a Food and Drug Administration-approved YAP-TEAD inhibitor in preclinical glioblastoma models; and is currently collaborating with other groups from academia and industry to translate YAP-TEAD inhibitors into early clinical trials. A second and related focus of the lab is to elucidate the biology of human glial development, and its aberrant re-expression in disease states such as brain tumors.

Scientists in this research area include:

• Nadejda (Nadia) Tsankova, MD, PhD

The inherent genetic instability of cancer cells and their resulting adaptive abilities is a major reason why gliomas inevitably recur following treatment and are ultimately fatal. A greater understanding of the cancer genome as a dynamic, three-dimensional structure will lead to the development of new strategies to address cancer evolution directly. We also seek to understand how current standard treatment regimes, such as radiation therapy and chemotherapy, interact with the cancer genome to influence the way in which tumor cells change through time and diversify in different compartments in the brain.

Scientists in this research area include:

• Raymund Yong, MD

Our research focuses on the characterization of the pharmacokinetic and pharmacodynamic properties of anticancer drugs for brain tumors. These studies have a common goal of understanding the variables that influence drug disposition and dynamics in the tumor. Through the use of detailed measurements of drug concentrations, we build physiologically-based models that provide mechanistic information and allow for model predictions to be made. The progression of preclinical studies may lead to new drug treatment strategies and means to optimize drug treatment regimens in patients.

Scientists in this research area include:

• Thomas O'Loughlin, PhD