Identifying Therapeutic Biomarkers of Proteasome Inhibitor Efficacy in Glioblastoma

Glioblastoma (GBM) is the most common malignant primary brain tumor, with a median survival of only 21 months. Despite decades of research, the prognosis for GBM patients remains poor, and treatment options are limited. Recently, proteasome inhibitors have emerged as a promising therapeutic modality; however, several clinical trials have shown that only a subset of GBM patients responds to this treatment, and it is still unclear why. Our lab has previously shown that some proteasome subunits may have pro-carcinogenic functions outside their canonical roles in the ubiquitin-proteasome system, which may explain why this therapy does not work in all patients. Thus, this project aims to utilize unbiased CRISPR-Cas9 screening techniques to determine which proteasome subunits display these novel functions. By identifying which proteasome subunits harbor extra-proteasomal driver functions, we may be able to elucidate therapeutic biomarkers and ultimately increase the pool of patients that could benefit from this promising therapy.