Adult brain cancer continues to be a significant challenge to clinicians and over 20,000 cases are diagnosed per year. Because the prognosis for individuals with glioblastoma, the most common type of brain cancer, remains poor, it is of critical importance that new therapies be developed. This proposal requests funds to support a research program that integrates physical sciences concepts and approaches with basic and clinical cancer biology research strategies to explore the role of cell intrinsic and external force in GBM aggression. The hope is that this interdisciplinary approach will offer a new paradigm with which to clarify the basis for the invasive and treatment resistant phenotype of high grade GBMs, and by so doing reveal new avenues for developing novel diagnostics, prognostics and therapies.