The major goals of the Neuro-Oncology (NRO) Program are to understand the molecular mechanisms that are involved in the etiopathogenesis and progression of primary brain tumors and metastases to brain, and to use this knowledge to better manage patients with these malignancies; they belong to a high incidence/high mortality population in the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) catchment area.

The research of the NRO Program centers particularly on malignant gliomas, including glioblastoma, and breast and lung cancer brain metastases.

Specific Aims

Aim 1: Determine the role of cancer stem-like cells in tumor initiation and/or progression through studying signaling pathways and interactions with other cell types present in the tumor microenvironment and normal brain. Areas of particular focus are malignant gliomas, including glioblastoma, and breast and lung cancer brain metastases. In all of these, cancer stem-like cells appear to play a particularly important role. The aim reflects a focus on mechanisms regulating participation of these cells in cancer initiation and progression, and those that are potential targets for therapeutics.

Aim 2: Develop novel therapeutic approaches for these difficult-to-treat cancers based on a) biophysical forces employed to target cancer (e.g., irreversible electroporation and electromagnetic fields), b) biotherapeutics in the form of proteinaceous targeted cytotoxins, oncolytic viruses and antibody targeting of tumor-associated vasculature, c) disrupting signaling between cancer cells and other cells in the tumor microenvironment, and d) drug delivery specifically to cells of the tumor microenvironment. The new approaches to this treatment theme reflect broad interest in identifying new therapeutic strategies including those that lead to improved delivery of drugs to the CNS to better manage both primary and metastatic brain tumors.

Aim 3: Conduct innovative clinical interventions which will affect the course of the disease and the well-being of patients. The aim leverages the rich history of early-phase clinical brain tumor research at Wake by the program leaders through long-standing participation in the Adult Brain Tumor Consortium (ABTC), other national brain tumor collaborations, as well as investigator-initiated trials.

Research Project Highlights