Research

Antiangiogenic therapy

Antiangiogenic therapy uses drugs designed to prevent the formation of new blood vessels to stop cancer growth. Glioblastoma, the most common and aggressive adult primary brain cancer, is particularly resistant to antiangiogenic therapy. We have developed a preclinical model of antiangiogenic therapy resistance. This mouse model has allowed us to evaluate multiple mechanisms of resistance, as well as potential therapeutic approaches to delay or overcome this resistance. Several novel combination therapies investigated in our laboratory have been translated into clinical trials.

Targeted therapies

Under the leadership of John de Groot, M.D., we created a robust clinically annotated prospective tumor profiling program, known as PROACTIVE. More than 1,400 patients have been enrolled in the protocol, and nearly 900 have been molecularly characterized in collaboration with the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy. Many of these patients have been enrolled into molecularly-driven clinical trials in Neuro-Oncology and in Phase I clinical trials in the Institute for Clinical Trials.

Data from this program has also enabled our team to collaborate with others both inside and outside of MD Anderson to evaluate existing drugs against a panel of glioma stem cell lines and identify drug-sensitivity-genomic correlations and biomarkers of resistance. PROACTIVE was designed so the data could be integrated into the Adaptive Patient-Oriented Longitudinal Learning and Optimization (APOLLO) research platform, part of MD Anderson’s Moon Shots program.

Clinical research

The de Groot lab has translated many findings from “bench to bedside” through the development of clinical trials, including multiple clinical trials evaluating the therapeutic efficacy of antiangiogenic agents in patients with newly diagnosed and recurrent glioblastoma. We have pioneered alternative dosing schedules of antiangiogenic therapies as a novel mechanism of delaying resistance and identified STAT3 as an important mediator of resistance in both circulating myeloid cells as well as in tumor cells.

The de Groot lab has also played a key role in developing biomarker-driven clinical trials and immunotherapy clinical trials. We developed a unique “treat-biopsy-treat” paradigm for a clinical trial evaluating pembrolizumab (KEYTRUDA®) for glioblastoma. It is the first and only clinical trials of its kind in the field of checkpoint inhibitors for glioblastoma.